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Moret, Francesca (2013) Nanovehicles for medical use: an in vitro evaluation
of cytotoxicity and drug delivery efficiency.
[Ph.D. thesis]

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Abstract (english)

The recent progresses offered by nanotechnology in the manipulation of matter lead to the development of several nanoparticles (NPs) and nanodevices for medical applications. In oncology, nanosized objects are particularly attractive as drug delivery systems since it is expected that engineered nanovehicles of appropriate size and functionalised with specific ligands/antibodies will improve the efficacy and selectivity of cancer therapies by exploiting both the passive and active mechanism of tumour targeting. The use of delivery systems is particularly appealing in those therapies in which the administration of the drug in aqueous formulations leads to drug aggregation with decreased activity or scarce bioavailability and tumour selectivity. This is the case of most of the photosensitizers used in photodynamic therapy (PDT), which display hydrophobicity and poor selective accumulation in malignant tissues. In the last decades, PDT is emerging as a promising cancer treatment modality in alternative to conventional therapies, which often demonstrate systemic drug toxicity and multidrug-resistance phenomena. PDT is based on the administration of a photosensitizer (PS) that accumulates in the tumour and after activation with light of appropriate wavelengths, reacts with surrounding molecular oxygen leading to the formation of cytotoxic reactive oxygen species (ROS) with consequent cellular and vasculature damages.
In this PhD thesis, three different nanosystems, namely, liposomes, poly-(D,L-lactide-co-glycolide) nanoparticles (PLGA NPs) and ORganically Modified SILica nanoparticles (ORMOSIL NPs) were considered for the delivery of the second generation PS meta-tetra(hydroxyphenyl)chlorin (m-THPC, Temoporfin) to cancer cells in vitro. In particular, drug delivery efficiency, dark and phototoxicity of the m-THPC nanoparticle-based formulations were evaluated. To improve m-THPC bioavailability and tumour selectivity, in the design of the nanovehicles PEGylation and targeting of NPs were considered as essential strategies in order to prolong NP circulation in the bloodstream and exploit active mechanisms of tumour targeting.
For the delivery of m-THPC using unilamellar liposomes, four different PEGylated liposomal formulations (trade name Fospeg®, provided by Biolitec Research) in which the length (PEG750, PEG2000, PEG5000) and the density (2%, 8%) of PEG were varied, were tested in vitro in normal lung fibroblasts CCD-34Lu and in cancer A549 lung epithelial cells. Compared to drug delivered in the standard solvent (Foscan®, ethanol/PEG 400/water (20:30:50, by vol.)), liposomal m-THPC showed a decreased intracellular uptake in both cell lines, but the presence of the delivery system highly reduced the dark cytotoxicity of the drug. The reduction of the PS dark toxicity increased with the increasing of PEG density on liposome surface, while the length of PEG chains did not affect significantly the toxic effect of m-THPC in the dark. However, photo-toxicity measured in A549 cells was only slightly affected by the reduced uptake of m-THPC delivered by Fospeg®, and the efficiency of PDT-induced cell killing was comparable among the different liposomal formulations. Interestingly, the intracellular localization of m-THPC delivered as Fospeg® or Foscan® was the same (Golgi apparatus and endoplasmic reticulum) suggesting drug release from liposomes, especially in the presence of the serum proteins, being m-THPC only physically entrapped within liposomes. m-THPC release was confirmed by the fact that liposomes covalently labelled with rhodamine were effectively were taken up by cells but, differently from m-THPC, localized in the acidic compartments of the cells. In spite of m-THPC release from liposomes, the Fospeg® formulation was exploited to target actively cancer cells by liposome conjugation with folic acid (FA), being FA-receptors (FRs) over-expressed in several human tumours. Thus, specific uptake and photo-toxicity of FA-targeted liposomes (FA-Fospeg) with respect to liposomes of the same composition but lacking FA (un-targeted Fospeg) was evaluated in KB (FR-positive) and in A549 (FR-negative) cells. The uptake of m-THPC delivered as FA-Fospeg was twice that of un-targeted Fospeg in KB cells; however only a modest fraction (~ 15%) of the targeted vehicle was effectively internalized by FR-mediated endocytosis while nonspecific internalization remained the prevailing mechanism of liposomes uptake in both cell lines. The improved m-THPC uptake obtained with FA-Fospeg in FR over-expressing cells translated into a 1.5 higher photo-induced toxicity.
A novel formulation of bare and PEGylated PLGA NPs in which m-THPC was physically entrapped were synthesized (Prof J. Kos, University of Ljubljana) and evaluated in vitro and in vivo for phototherapy and fluorescence-based tumour imaging applications. In vitro studies carried out on A549, MCF10A neo T (breast cancer cells) and U937 (lymphoma derived pro-monocytic cells) cell lines, showed reduced uptake of PEGylated NPs with respect to non PEGylated NPs. As for Fospeg®, the use of the delivery system led to a significant reduction of m-THPC dark toxicity.. As expected for PEGylated NPs, the efficiency of cell internalization of m-THPC entrapped in PEG PLGA was reduced by 50% with respect to that in the standard solvent, but surprisingly cytotoxicity induced in irradiated A549 cells was quite comparable. At 24 h post-injection in vivo biodistribution of bare and PEGylated PLGA NPs compared to Foscan® was assessed in mice, showing very similar drug accumulation in the major organs but reduced skin uptake for both NP formulations. Thus, even if m-THPC release in the presence of serum proteins was measured in vitro, PEGylated PLGA NPs appeared potentially useful as stealth and biodegradable PS delivery systems.
The premature release of the PS from the delivery system was completely avoided with the covalent link of m-THPC to the silane matrix of highly PEGylated ORMOSIL NPs (Prof. F. Mancin, University of Padova). This type of NPs exhibited a very low extent of cell internalization in vitro due to their high degree of PEGylation, making NP targeting an essential prerequisite to enhance intracellular drug delivery. In addition to FA, the RGD peptide and the antibody Cetuximab, which bind respectively the integrin α5ß3 receptor and epidermal growth factor receptor (EGFR), were exploited as targeting agents for ORMOSIL NPs and the specific uptake and photo-toxicity of m-THPC delivered by conjugated NPs were evaluated in vitro. The study revealed how the characteristics of the targeting agents are of crucial importance in determining the performances of targeted PEGylated nanosystems. In fact, the hydrophobic FA was very likely buried in the PEG layer and was unable to drive the selective uptake of ORMOSIL NPs while RGD peptide and Cetuximab antibody displayed some selectivity toward cells over-expressing their receptors (HUVEC cells over-expressing integrin α5ß3 receptors and A431 cells over-expressing EGFR). Unfortunately, the enhanced and selective uptake of m-THPC obtained by the two latter targeted ORMOSIL NPs was not accompanied by efficient and selective photo-induced cytotoxicity; it appeared that the selectivity of NP uptake was achieved in scarce drug cell loading conditions, determining only low PDT efficacy.
The assessment of the biocompatibility of NPs is of fundamental importance for their safe use in nanomedicine. Since ORMOSIL NPs are not well characterised from this point of view, a toxicological characterization of empty ORMOSIL NPs were carried out in vitro in normal (CCD-34Lu) and cancer (A549, NCIH-2347) lung cells. The study included traditional cell viability and cytotoxicity tests (MTS test, LDH release assay, ROS production, cell membrane permeabilization measurements and electron microscopy analyses) in combination with a genome-wide analysis of gene expression profiles of cells exposed to NPs. The results pointed out that different types of cells respond quite differently to NPs and PEGylation of NPs highly affected the cytotoxicity profiles. PEGylation of ORMOSIL NPs completely abolished the toxicity of the nanosystem in CCD-34Lu and NCIH-2347 cells. On the contrary PEG ORMOSIL NPs induced necrotic cell death of A549 by increasing the permeability of the plasma membrane. At sub-lethal concentrations alteration of gene expression and inflammation were measured in A549 cells exposed to. The different response to PEG NPs is very likely explained considering the peculiarity of the cell type and the particular interaction of NPs with cell and internalization mechanisms. In fact, it was shown clearly that NPs internalized in A549 cells localized in and affected the morphology and the functioning of pulmonary surfactant containing lamellar bodies, peculiar of alveolar type II cells of which A459 cells represents an in vitro models.

Abstract (italian)

Il recente progresso apportato dalla nanotecnologia nella manipolazione della materia ha portato al conseguente sviluppo di diversi tipi di nanoparticelle e nanodevices per applicazioni biomediche. In campo oncologico, oggetti dalle dimensioni nanometriche si sono dimostrati particolarmente interessanti in qualità di sistemi per la veicolazione di farmaci, poiché si presume che l’ingegnerizzazione dei nanoveicoli e la loro funzionalizzazione con specifici ligandi/anticorpi possa portare ad un miglioramento dell’efficacia e della selettività delle terapie antitumorali sfruttando meccanismi di targeting del tumore sia passivi che attivi. L’utilizzo di sistemi di veicolazione è particolarmente importante nel caso di terapie nelle quali la somministrazione dei farmaci in formulazioni acquose conduce a fenomeni di aggregazione con conseguente diminuzione di attività e di disponibilità nel circolo sanguineo, o nel caso di farmaci con scarsa selettività per il tumore. Appartengono a queste categorie la maggior parte dei fotosensibilizzanti utilizzati in terapia fotodinamica (PDT), poiché farmaci di natura idrofobica e con scarsa selettività di accumulo nei tessuti maligni. Negli ultimi decenni, la PDT si è dimostrata una promettente tecnica di trattamento del cancro in alternativa alle terapie convenzionali che invece generalmente dimostrano alta tossicità sistemica e fenomeni di farmaco-resistenza. La PDT si basa sulla somministrazione di un fotosensibilizzante (PS) che accumulatosi nel tumore, e dopo essere stato attivato con opportune lunghezze d’onda di luce, è in grado di reagire con l’ossigeno molecolare che lo circonda generando specie reattive dell’ossigeno (ROS) altamente citotossiche con conseguente danno cellulare e vascolare. In questa tesi di dottorato, tre diversi nanosistemi quali liposomi, nanoparticelle PLGA (poly-(D,L-lactide-co-glycolide)) e nanoparticelle di silice organicamente modificata (ORMOSIL), sono stati presi in considerazione per la veicolazione del fotosensibilizzante di seconda generazione meta-tetra(hydroxyphenyl)chlorin (m-THPC, Temoporfin) in cellule tumorali in vitro. In particolare, sono state valutate l’efficienza di veicolazione del farmaco, la tossicità buia e fotoindotta delle diverse formulazioni di m-THPC. Per migliorare la biodisponibilità e la selettività per il tumore della m-THPC, nella progettazione dei nanoveicoli sono state considerate quali strategie essenziali la pegilazione e il targeting delle particelle, in modo da prolungare la circolazione dei nanosistemi nel flusso sanguineo e in modo da sfruttare meccanismi attivi di targeting del tumore.
Per la veicolazione della m-THPC utilizzando liposomi unilamellari sono state saggiate in vitro quattro diverse formulazioni liposomiali pegilate (Fospeg®, fornito dalla ditta Biolitec Research) con lunghezza (PEG750, PEG2000, PEG5000) e densità del PEG (2%, 8%) variabili, utilizzando come linee cellulari fibroblasti di polmone normali (CCD-34Lu) e cellule tumorali di epitelio polmonare (A549). Se paragonate al farmaco somministrato in forma libera in soluzione (Foscan®, etanolo/PEG 400/acqua (20:30:50, vol/vol)), le formulazioni liposomiali di m-THPC hanno mostrato una ridotta internalizzazione in entrambe le linee cellulari, ma nello stesso tempo la presenza del sistema di veicolazione ha portato alla significativa riduzione della tossicità buia del farmaco. La riduzione della tossicità buia del farmaco è risultata proporzionale all’aumento della densità di PEG sulla superficie del liposoma mentre la lunghezza delle catene di PEG sembra essere ininfluente nel limitare l’effetto tossico della m-THPC al buio. Comunque, la ridotta internalizzazione della m-THPC veicolata tramite Fospeg® influenza in modo solo parziale la fototossicità misurata in cellule A549, mentre l’efficienza d’induzione di mortalità in seguito a trattamento fotodinamico è risultata paragonabile tra le diverse formulazioni saggiate. Indipendentemente dalla veicolazione tramite Fospeg® o Foscan®, è stata riscontrata la medesima localizzazione intracellulare della m-THPC (apparato del Golgi e reticolo endoplasmatico) suggerendo il possibile rilascio del farmaco dalla formulazione liposomiale in presenza di proteine del siero, essendo la m-THPC solamente fisicamente intrappolata all’interno dei liposomi. Il rilascio della m-THPC è stato confermato dal fatto che liposomi nei quali viene legata covalentemente rodamina vengono effettivamente internalizzati dalle cellule e, differentemente dalla m-THPC, si accumulano nei compartimenti acidi intracellulari.
Nonostante il rilascio del fotosensibilizzante dai liposomi, la formulazione Fospeg® è comunque stata utilizzata per veicolare selettivamente la m-THPC in cellule cancerose tramite la coniugazione dei liposomi con acido folico, essendo i recettori del folato sovraespressi in diversi tumori umani. Quindi sono state valutate l’internalizzazione specifica e la fototossicità di liposomi coniugati con folato (liposomi folato) rispetto a liposomi della stessa composizione ma privi di acido folico (liposomi non coniugati) in cellule KB e A549, rispettivamente positive e negative per l’espressione di recettori del folato. In cellule KB, l’internalizzazione della m-THPC si è rivelata doppia in caso di veicolazione con liposomi folato, malgrado solo una modesta parte (~15%) dei nanosistemi coniugati con folato siano effettivamente internalizzati tramite meccanismi di endocitosi mediata da recettore, essendo invece un’internalizzazione di tipo aspecifico il meccanismo prevalente per l’internalizzazione dei liposomi in entrambe le linee cellulari saggiate. In ogni caso, all’aumentato accumulo di m-THPC ottenuto tramite la veicolazione con Fospeg coniugato con folato in cellule che sovra esprimono il recettore, ne è conseguita una tossicità dopo irradiamento aumentata di circa 1.5 volte.
Riguardo invece la veicolazione di m-THPC tramite particelle PLGA, formulazioni nude o pegilate sono state sintetizzate (Prof. J. Kos, Università di Lubiana) e saggiate sia in vitro che in vivo per la loro potenziale applicazione in fototerapia o in diagnosi dei tumori, sfruttando la fluorescenza del fotosensibilizzante fisicamente intrappolato all’interno delle particelle. Studi in vitro condotti su cellule A549, MCF10A neo T (derivate da tumore del seno) e U937 (cellule pro-monocitiche derivate da linfoma), hanno mostrato una ridotta internalizzazione della formulazione di m-THPC pegilata rispetto a quella nuda. Anche con particelle PLGA e come già visto per il Fospeg®, l’utilizzo di un sistema di veicolazione porta alla significativa riduzione della citotossicità buia della m-THPC. L’efficienza d’internalizzazione del fotosensibilizzante veicolato tramite particelle PLGA pegilate viene ridotta circa del 50% rispetto alla sua veicolazione nella formulazione standard ma sorprendentemente l’effetto citotossico indotto in cellule A549 irradiate è quasi paragonabile. La biodistribuzione della m-THPC (veicolata tramite nanoparticelle PLGA nude o pegilate o nella formulazione standard) è stata valutata 24 ore dopo la sua iniezione in topi, mostrando una simile distribuzione nei vari organi ma una significativa riduzione dell’accumulo a livello epidermico per entrambe le formulazioni nanoparticellari. Quindi, nonostante anche per le particelle PLGA pegilate sia stato misurato il rilascio di m-THPC in presenza di proteine sieriche, esse appaiono un buon sistema di veicolazione di fotosensibilizzanti soprattutto per le loro caratteristiche ‘stealth’ e per la loro biodegradabilità.
Il rilascio prematuro del fotosensibilizzante è stato invece completamente limitato con il legame covalente della m-THPC alla matrice silanica di particelle ORMOSIL altamente pegilate (Prof. F. Mancin, Università di Padova). Tuttavia questo tipo di particelle ha mostrato un’internalizzazione intracellulare estremamente bassa derivata dall’elevato grado di pegilazione, ponendo come requisito essenziale il targeting delle particelle. In qualità di agenti di targeting per le particelle ORMOSIL pegilate sono stati valutati, oltre al folato, anche il peptide ciclico RGD e l’anticorpo Cetuximab, essendo questi ultimi in grado di legarsi rispettivamente ad integrine α5ß3 e al recettore del fattore di crescite dell’epidermide (EGFR). L’internalizzazione selettiva e la fototossicità della m-THPC veicolata tramite le tre diverse nanoparticelle funzionalizzate sono state valutate in vitro in opportuni sistemi cellulari. Tale studio ha mostrato come le caratteristiche dell’agente di targeting influenzino in modo sostanziale la selettività di tali nanosistemi pegilati. Infatti, mentre il folato altamente idrofobico si ripiega verosimilmente verso la corona di PEG rendendosi inefficace nel guidare selettivamente le particelle ORMOSIL, il peptide RGD e l’anticorpo Cetuximab hanno mostrato una certa selettività nei confronti di cellule sovraesprimenti i rispettivi recettori (cellule HUVEC sovraesprimenti recettori per le integrine α5ß3 e cellule A431 sovraesperimenti EGFR). Tuttavia, l’aumentato accumulo selettivo della m-THPC ottenuto tramite la coniugazione delle nanoparticelle con RGD e Cetuximab non ha portato ad una conseguente aumentata efficienza e selettività nell’induzione di citotossicità in seguito ad irradiamento. Tale risultato è verosimilmente imputabile al fatto che la selettività di accumulo delle nanoparticelle viene raggiunta in condizioni nelle quali la disponibilità del farmaco nelle cellule è troppo bassa, con conseguente scarsa efficacia dopo trattamento fotodinamico.
La valutazione della biocompatibilità delle nanoparticelle risulta di fondamentale importanza per un’applicazione sicura della nanotecnologia in campo medico. Quindi, poiché le nanoparticelle ORMOSIL non sono ancora state ben caratterizzate da tale punto di vista, un loro profilo tossicologico è stato tracciato in vitro in cellule polmonari normali (CCD-34Lu) e tumorali (A549, NCIH-2347). Nello studio sono stati combinati esperimenti tradizionali di valutazione della vitalità cellulare e della citotossicità (test MTS, saggio del rilascio di LDH, valutazione della produzione di ROS, misure di permeabilizzazione di membrana, analisi di microscopia elettronica) con un’analisi dei profili di espressione genica estesa all’intero genoma di cellule esposte alle nanoparticelle. I risultati hanno mostrato come diversi tipi di cellule rispondono in modo abbastanza differente all’esposizione alle nanoparticelle e come la pegilazione influisce fortemente sui profili di citotossicità. Infatti, la pegilazione delle particelle ORMOSIL è in grado di abolire completamente la tossicità dei nanosistemi in cellule CCD-34Lu e NCIH-2347 mentre le stesse particelle pegilate inducono morte per necrosi in cellule A549, aumentandone la permeabilità di membrana. Inoltre nelle medesime cellule, concentrazioni sub-letali di nanoparticelle inducono infiammazione e alterazione dell’espressione genica. La differente risposta all’esposizione alle nanoparticelle pegilate delle cellule A549 è spiegabile considerando la peculiarità di questo tipo cellulare, e in particolare l’interazione delle particelle stesse con le cellule e il loro meccanismo d’internalizzazione. Infatti, è stato mostrato in modo chiaro che le nanoparticelle vengono internalizzate in corpi lamellari contenenti il surfattante polmonare, peculiari di cellule alveolari di tipo II, delle quali le cellule A549 rappresentano un modello in vitro. Tale accumulo delle nanoparticelle nei corpi lamellari porta alla modifica della morfologia degli stessi e una pesante alterazione della loro funzionalità.

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EPrint type:Ph.D. thesis
Tutor:Celotti, Lucia
Supervisor:Reddi, Elena
Data di deposito della tesi:24 April 2013
Anno di Pubblicazione:24 April 2013
Key Words:liposomes, ORMOSIL nanoparticles, PLGA nanoparticles, drug delivery, photodynamic therapy, nanotoxicology. liposomi, nanoparticelle ORMOSIL, nanoparticelle PLGA, delivery di farmaci, terapia fotodinamica, nanotossicologia
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/15 Biologia farmaceutica
Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Struttura di riferimento:Dipartimenti > Dipartimento di Biologia
Codice ID:6107
Depositato il:16 Oct 2013 10:31
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Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

Albanese A, Tang PS, Chan WCW, “The effect of nanoparticle size, shape and surface chemistry on biological systems”, 2012, Annu Rev Biomed Eng, 14, 1-16. Cerca con Google

Allison BA, Pritchard PH, Levy JG, “Evidence for low-density lipoprotein receptor-mediated uptake of benzoporphyrin derivative”, 1994, Br J Cancer, 69, 883-839. Cerca con Google

Allison RR, Downie GH, Cuenca R, Hu XH, Childs CJH, Sibata CH, “Photosensitizers in clinical PDT”, 2004, Photodyn Ther, 1, 27-42. Cerca con Google

Allison RR, Bagnato VS, Cuenca R, Downie GH, Sibata CH, “The future of photodynamic therapy in oncology”, 2006, Future Oncol, 2, 53-71. Cerca con Google

Agostinis P, Berg K, Cengel KA, Foster TH, Girotti AW, Gollnick SO, Hahn SM, Hamblin MR, Juzeniene A, Kessel, Korbelik M, Moan J, Mroz P, Nowis D, Piette J, Wilson BC, Golab J, “Photodynamic therapy of cancer: an update”, 2011, CA Cancer J Clin, 61, 250-281. Cerca con Google

Aguilar ZP, “Nanomaterials for medical applications”, 10/2012; Edition: 1st, Publisher: Elsevier, ISBN: 978-0-12-385089-8. Cerca con Google

Ahmed N, Fessi H, Elaissari A, “Theragnostic application of nanoparticles in cancer”, Drug Discov Today, 2012, 17, 928-934. Cerca con Google

Allen TM, Cullis PR, “Drug delivery systems: entering the mainstream”, 2004, Science, 303, 1818-1822. Cerca con Google

Amoozgar Z, Yeo Y, “Recent advances in stealth coating of nanoparticle drug delivery systems”, 2012, Wires Nanomed Nanotech, 4, 219-233. Cerca con Google

Arora S., Rajwade JM, Paknikar KM, “Nanotoxicology and in vitro studies: the need of the hour”, 2012, Toxicol Appl Pharm, 258, 151-165. Cerca con Google

Ashley CE, Carnes EC, Phillips GK, Padilla D, Durfee PN, Brown PA, Hanna TN, Liu J, Phillips B, Carter MB, Carroll NJ, Jiang X, Dunphy DR, Willman CL, Petsev DN, Evans DG, Parikh AN, Chackerian B, Wharton W, Peabody DS, Brinker CJ, “The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers”, 2011, Nat Mater, 10, 389-397. Cerca con Google

Ball DJ, Vernon DI, Brown SB, “The high photoactivity of m-THPC in photodynamic therapy. Unusually strong retention of m-THPC by RIF-1 cells in culture”, 1999, Photochem Photobiol, 69, 360-363. Cerca con Google

Bangham JA, Lea EJ, “The interaction of detergents with bilayer lipid membranes”, 1978, Biochim Biophys Acta, 511, 388-396. Cerca con Google

Berlanda J, Kiesslich T, Engelhardt V, Krammer B, Plaetzer K, “Comparative in vitro study on the characteristics of different photosensitizers employed in PDT”, 2010, J Photochem Photobiol B, 100, 173–180. Cerca con Google

Bhuvaneswari R, Gan YY, Soo KC, Olivo M, “The effect of photodynamic therapy on tumor angiogenesis”, 2009, Cell Mol Life Sci, 66, 2275–2283. Cerca con Google

Bonnet R, Djelai BD, A Nguyen, “Physical and chemical studies related to the development of m-THPC (FOSCAN®) for the photodynamic therapy (PDT) of tumours”, 2001, J Phorphyrins Phtalocyanines, 5, 652-661. Cerca con Google

Borm PJA, Kreylin W, “Toxicological hazards of inhaled nanoparticles-potential implications for drug delivery”, 2004, J Nanosci Nanotechno, 4, 521-531. Cerca con Google

Bourdon O, Laville I, Carrez D, Croisy A, Fedel P, Kasselouri A, Prognon P, Legrand P, Blais J, “Biodistribution of meta-tetra(hydroxyphenyl)chlorin incorporated into surface-modified nanocapsules in tumor-bearing mice”, 2002, Photochem Photobiol Sci, 1, 709–714. Cerca con Google

Bovis MJ, Woodhams JH, Loizidou M, Scheglmann D, Bown SG, MacRobert AJ, “Improved in vivo delivery of m-THPC via pegylated liposomes for use in photodynamic therapy”, 2012, J Control Release, 157, 196-205. Cerca con Google

Buchholz J, Kaser-Hotz B, Khan T, Rohrer BC, Melzer K, Schwendener RA, Roos M, Walt H, “Optimizing photodynamic therapy: in vivo pharmacokinetics of liposomal meta-(tetra-hydroxyphenyl)chlorin in feline squamous cell carcinoma”, 2005, Clin Cancer Res, 11, 7538–7544. Cerca con Google

Burgaj AM, “Targeted photodynamic therapy – a promising strategy of tumour treatment”, 2011, Photochem Photobiol Sci, 10, 1097-1109. Cerca con Google

Calzavara-Pinton PG, Venturini M, Sala R, “Photodynamic therapy: update 2006. Part 1”, 2006, Photochem Photobiol, 21, 293-302. Cerca con Google

Canelas DA, Herlihy KP, De Simone JM, “Top-down particle fabrication: control of size and shape for diagnostic imaging and drug delivery”, 2009, Wires Nanomed Nanotech, 1, 391–404. Cerca con Google

Carstensen H, Muller RH, Muller BW, “Particle-size, surface hydrophobicity and interaction with serum of parental fat emulsions and model-drug carriers as parameters related to RES uptake”, 1992, Clin Nutr, 11, 289-297. Cerca con Google

Castano AP, Demidova TN, Hamblin MR, “Mechanisms in photodynamic therapy: Part two-Cellular signalling, cell metabolism and modes of cell death”, 2005, Photodiagn Photodyn Ther, 2, 1-23. Cerca con Google

Cattaneo AG, Gornati R, Sabbioni E, Chiriva-Internati M, Cobos E, Jenkins MR, Bernardini G, “Nanotechnology and human health: risks and benefits”, 2010, J Appl Toxicol, 30, 730-744. Cerca con Google

Cedervall T, Lynch I, Lindman S, Berggård T, Thulin E, Nilsson H, Dawson KA, Linse S, “Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles”, 2007, Proc Natl Acad Sci USA, 104, 2050-2055. Cerca con Google

Chatterjee DK, Yong Z, “Upconverting nanoparticles as nanotransducers for photodynamic therapy in cancer cells”, 2008, Nanomedicine (London), 3, 73-82. Cerca con Google

Chen J, Zhao JX, “Upconversion nanomaterials: synthesis, mechanism, and applications in sensing”, 2012, Sensors Basel, 12, 2414-2435. Cerca con Google

Chen XJ, Sanchez-Gaytan BL, Qian Z, Park SJ, “Noble metal nanoparticles in DNA detection and delivery”, 2012, Wires Nanomed Nanobiotechnol, 4, 273-290. Cerca con Google

Chen W, Zhang J, “Using nanoparticles to enable simultaneous radiation of photodynamic therapy for cancer treatment”, 2006, J Nanosci Nanotechnol, 6, 1159-1166. Cerca con Google

Cheng Z, Al Zaki A, Hui JZ, Muzykantov VR, Tsourkas A, “Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities”, 2012, Science, 338, 903-910. Cerca con Google

Clift MJD, Stone V, “Quantum Dots: an insight and perspective of their biological interaction and how this relates to their relevance for clinical use”, 2012, Theranostics, 2, 668-680. Cerca con Google

Dysart JS, Patterson MS, “Characterization of Photofrin photobleaching for singlet oxygen dose estimation during photodynamic therapy of MLL cells in vitro”, 2005, Phys Med Biol, 50, 2597–2616. Cerca con Google

Collaud S, Juzeniene A, Moan J, Lange N, “On the selectivity of 5-aminolevulinic acid-induced protoporphyrin IX formation”, 2004, Curr Med Chem Anti-Canc Agents, 4, 301-316. Cerca con Google

Compagnin C, Baù L, Mognato M, Celotti L, Miotto G, Arduini M, Moret F, Fede C, Selvestrel F, Rio Echevarria IM, Mancin F, Reddi E, “The cellular uptake of meta-tetra(hydroxyphenyl)chlorin entrapped in organically modified silica nanoparticles is mediated by serum proteins”, 2009, Nanotechnology, 20, 345101. Cerca con Google

Couleaud P, Morosini V, Frochot C, Richeter S, Raehma L, Durand JO, “Silica-based nanoparticles for photodynamic therapy applications”, 2010, Nanoscale, 2, 1083-1095. Cerca con Google

Cui S, Chen H, Zhu H, Tian J, Chi X, Qian Z, Achilefu S, Gu Y, “Amphiphilic chitosan modified upconversion nanoparticles for in vivo photodynamic therapy induced by near-infrared light”, 2012, J Mater Chem, 22, 4861-4873. Cerca con Google

Curtis J, Greenberg M, Kester J, Phillips S, Krieger G, “Nanotechnology and nanotoxicology: a primer for clinicians”, 2006, Toxicol Sci, 25, 245-260. Cerca con Google

Da Silva AR, Inada NM, Rettori D, Baratti MO, Vercesi AE, Jorge RA, “In vitro photodynamic activity of chloro(5,10,15,20-tetraphenylporphyrinato)indium(III) loaded-poly(lactide-co-glycolide) nanoparticles in LNCaP prostate tumour cells”, 2009, J Photochem Photobiol B, 94, 101-112. Cerca con Google

Danhier F, Ansorena E, Silva JM, Coco R, Le Breton A, Préat V, “PLGA-based nanoparticles: An overview of biomedical applications”, 2012, J Control Release, 161, 505-522. Cerca con Google

D’Cruz AK, Robinson MH, Biel MA, “mTHPC-mediated photodynamic therapy in patients with advanced, incurable head and neck cancer. A multicenter study of 128 patients”, 2004, Head Neck, 26, 232-240. Cerca con Google

D’Hallewin MA, Kochetkov D, Viry-Babel Y, Leroux A, Werkmeister E, Dumas D, Gräfe S, Zorin V, Guillemin F, Bezdetnaya L, “Photodynamic therapy with intratumoral administration of lipid-based mTHPC in a model of breast cancer recurrence”, 2008, Lasers Surg Med, 40, 543–549. Cerca con Google

Donaldson K, Stone V, Tran CL, Kreyling W, Borm PJA, “Nanotoxicology”, 2004, Occup Environ Med, 61, 727-728. Cerca con Google

Dos SN, Allen C, Doppen AM, Anantha M, Cox KA, Gallagher RC, Karlsson G, Edwards K, Kenner G, Samuels L, Webb MS, Bally MB, “Influence of poly-(ethyleneglycol) grafting density and polymer length on liposomes: relating plasma circulation lifetimes to protein binding”, 2007, Biochim Biophys Acta, 1768, 1367-1377. Cerca con Google

Dougherty TJ, Gomer CJ, Henderson BW, Jori G, Kessel D, Korbelik M, Moan J, Peng Q, “Photodynamic therapy”, 1998, J Natl Cancer Inst, 90, 889–905. Cerca con Google

Duncan R, Gaspar R, “Nanomedicine(s) under the microscope”, 2011, Mol Pharmaceutics, 8, 2101-2141. Cerca con Google

Ebbesen M, Jensen TG, “Nanomedicine: techniques, potentials, and ethical implication”, 2006, J Biomed Biotechnol, 5, 1-11. Cerca con Google

Fadeel B, Garcia-Bennet AE, “Better safe than sorry: understanding the toxicological properties of inorganic manufactured for biomedical applications”, 2010, Adv Drug Del Rev, 62, 362-374. Cerca con Google

Fadel M, Kassab K, Fadeel DA, “Zinc phthalocyanine-loaded PLGA biodegradable nanoparticles for photodynamic therapy in tumor-bearing mice”, 2010, Lasers Med Sci, 25, 283-292. Cerca con Google

Ferrari M., “Cancer nanotechnology: opportunities and challenges”, Nat Rev Cancer, 2005, 5, 161-171. Cerca con Google

Friberg EJ, Čunderlìková B, Pettersen EO, Moan J, “pH effects on the cellular uptake of four photosensitizing drugs evaluated for use in photodynamic therapy of cancer”, 2003, Cancer Lett, 95, 73-80. Cerca con Google

Gabizon A, Horowitz AT, Goren D, Tzemach D, Shmeeda H, Zalipsky S, “In vivo fate of folate-targeted polyethylene-glycol liposomes in tumor-bearing mice”, 2003, Clin Cancer Res, 9, 6551–6559. Cerca con Google

Gabizon A, Horowitz AT, Goren D, Tzemach D, Mandelbaum-Shavit F, Qazen MM, Zalipsky S, “Targeting folate receptor with folate linked to extremities of Poly(ethylene glycol)-grafted liposomes: in vitro studies”, 1999, Bioconjugate Chem, 10, 289-298. Cerca con Google

Garnett MC, Kallinteri P, “Nanomedicine and nanotoxicology: some physiological principles”, 2006, Occup Med-Oxford, 56, 307-311. Cerca con Google

Gref R, Domb A, Quellec P, Blunk T, Muller RH, Verbavatz JM, Langer R, “The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres”, 1995, Adv Drug Deliver Rev, 16, 215-233. Cerca con Google

Gref R, Luck M, Quellec P, Marchand M, Dellacherie E, Harnisch S, Blunk T, Muller RH, “’Stealth’ corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein absorbtion”, 2000, Colloid Surf B-Biointerfaces, 18, 301-313. Cerca con Google

Gref R, Couvreur P, Barratt G, Mysiakine E, “Surface-engineered nanoparticles for multiple ligand coupling”, 2003, Biomaterials, 24, 4925-4937. Cerca con Google

Gu F, Zhang L, Teply BA, Mann N, Wang A, Rodovic-Moreno AF, Langer R, Forokhzad OC, “Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers”, 2008, Proc Natl Acad Sci USA, 105, 2586–2591. Cerca con Google

Hagens WI, Oomen AG, De Jong WH, Casee FR, Sips AJAM, “What do we (need to) know about the kinetic properties of nanoparticles in the body”, 2007, Regul Toxicol Pharm, 49, 217-229. Cerca con Google

Hamblin MR, Hasan T, “Photodynamic therapy: a new antimicrobial approach to infectious disease?”, 2004, Photochem Photobiol Sci, 3, 436-450. Cerca con Google

Hatakeyama H, Akita H, Harashima H, “A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma”, 2011, Adv Drug Deliver Rev, 63, 152–160. Cerca con Google

Hirsjarvi S, Passirani C, Benoit JP, “Passive and active tumour targeting with nanocarriers”, 2011, Curr Drug Discov Technol, 8, 188-196. Cerca con Google

Hofman JW, Carstens MG, Van Zeeland F, Helwig C, Flesch FM, Hennink WE, Van Nostrum CF, “Photocytotoxicity of mTHPC (temoporfin) loaded polymeric micelles mediated by lipase catalyzed degradation”, 2008, Pharmaceut Res, 25, 2065–2073. Cerca con Google

Hopper C, Krubler A, Lewis H, Tan IB, Putnam G, “mTHPC-mediated photodynamic therapy for early oral squamous cell carcinoma”, 2004, Int J Cancer, 111, 138-146. Cerca con Google

Huang YW, Wu CH, Aronstam RS, “Toxicity of transition metal oxide nanoparticles: recent insights from in vitro studies”, 2010, Materials, 3, 4842-4859. Cerca con Google

Idris NM, Gnanasammandhan MK, Zhang J, Ho PC, Mahendran R, Zhang Y, “In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers”, 2012, Nat Med, 18, 1580–1585. Cerca con Google

Ishida O, Maruyama K, Tanahashi H, Iwatsuru M, Sasaki K, Eriguchi M, Yanagie H, “Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo”, 2001, Pharm Res, 18, 1042–1048. Cerca con Google

Kawano K, Maitani Y, “Effects of polyethylen glycol spacer lenght and ligand density on folate receptor targeting of liposomal Doxorubicin in vitro”, 2011, J Drug Del, 160967. Cerca con Google

Khdair A, Handa H, Mao G, Panyam J, “Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro”, 2009, Eur J Pharm Biopharm, 71, 214-222. Cerca con Google

Kiesslich, T, Berlanda J, Plaetzer K, Krammer B, Berr F, “Comparative characterization of the efficiency and cellular pharmacokinetics of Foscan®- and Foslip®- based photodynamic treatment in human biliary tract cancer cell lines”, 2007, Photochem Photobiol Sci, 6, 619–627. Cerca con Google

Klesing, J, Wiehe A, Gitter B, Gräfe S, Epple M, “Positively charged calcium phosphate⁄polymer nanoparticles for photodynamic therapy”, 2010, J Mater Sci Mater Med, 21, 887–892. Cerca con Google

Kocbek P, Teskac K, Brozic P, Laniŝnik Rižner T, Gobec S, Kristl J, “Effect of free and in poly(e-caprolactone) nanoparticles incorporated new type 1 17ß-hydroxysteroid dehydrogenase inhibitors on cancer cells”, 2010, Curr Nanosci, 6, 69–76. Cerca con Google

Konan Y, Gurny R, Allèmann E, “State of the art in the delivery of photosensitizers for photodynamic therapy”, 2002, J Photochem Photobiol B, 66, 89-106. Cerca con Google

Kopelman R, Koo YL, Philbert M, Moffat BA, Reddy GR, McConville P, Hall DE, Chenevert TL, Bhojani MS, Buck SM, Rehemtulla A, Ross BD, “Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer”, 2005, J Magn Magn Mater, 293, 404-410. Cerca con Google

Korbelik M, “PDT-associated host response and its role in the therapy outcome”, 2006, Lasers Surg Med, 38, 500–508. Cerca con Google

Konan YN, Chevallier J, Gurny R, Allèman E, “Encapsulation of p-THPP into nanoparticles: cellular uptake, subcellular localization and effect of serum on photodynamic activity”, 2003, Photochem Photobiol, 77, 638-644. Cerca con Google

Krammer B, Plaetzer K, “ALA and its clinical impact, from bench to bedside”, 2008, Photochem Photobiol Sci, 7, 283-289. Cerca con Google

Kuai R, Yuan W, Qin Y, Chen H, Tang J, Yuan M, Zhang Z, He Q, “Efficient delivery of payload into tumor cells in a controlled manner by TAT and thiolytic cleavable PEG co-modified liposomes, 2010, Mol Pharmaceutics, 7, 1816-1826. Cerca con Google

Kumari A, Yadav SK, Yadav SC, “Biodegradable polymeric nanoparticles based drug delivery systems”, 2010, Colloids Surf B Biointerfaces, 75, 1–18. Cerca con Google

Lam S, Kostashuk EC, Coy EP, Laukkanen E, LeRiche CJ, Mueller HA, Szasz IJ, “A randomized comparative study of the safety and efficacy of photodynamic therapy using Photofrin II combined with palliative radiotherapy versus palliative radiotherapy alone in patients with inoperable obstructive non-small cell bronchogenic carcinoma”, 1987, Photochem Photobiol, 46, 893-897. Cerca con Google

Lammers T, Kiessling F, Hennink WE, storm G, “Drug targeting to tumours: principles, pitfalls, and (pre) clinical progress”, 2012, J Control Release, 161, 175-181. Cerca con Google

Lasalle HP, Dumas D, Gräfe S, D’Hallewin MA, Guillemin F, Bezdetnaya L, “Correlation between in vivo pharmakinetics, intratumoral distribution and photodynamic efficiency of liposomal mTHPC”, 2009, J Control Release, 134, 118–124. Cerca con Google

Levy JG, Obochi M, “New application in photodynamic therapy introduction, 1996, Photochem Photobiol, 64, 737-739. Cerca con Google

Lewinski N, Colvin V, Drezek R, “Cytotoxicity of nanoparticles”, 2008, Small, 4, 26-49. Cerca con Google

Lin MM, Kim do K, El Haj AJ, Dobson J, “Development of superparamagnetic iron oxide nanoparticles (SPIONS) for translation to clinical applications”, 2008, IEEE Trans Nanobioscience, 7, 298-305. Cerca con Google

Liu Z, Chen K, Davis C, Sherlock S, Cao Q, Chen X, Dai H, “Drug delivery with carbon nanotubes for in vivo cancer treatment”, 2008, Cancer Res, 68, 6652-6660. Cerca con Google

Longmire MR, Ogawa M, Choyke PL, Kobayashi H, “Biologically optimized nanosized molecules and particles: more than just size”, 2011, Bioconjugate Chem, 22, 993–1000. Cerca con Google

Lynch I, Dawson KA, “Protein-nanoparticle interactions”, 2008, Nano Today, 3, 40-47. Cerca con Google

Maeda H, Wu J, Sawa T, Matsumara Y, Hori K, “Tumour vascular permeability and the EPR effect in macromolecular therapeutics: a review”, 2000, J Control Release, 65, 271-284. Cerca con Google

Marchasin S, Wallerstein RO, “The treatment of iron-deficiency anemia with intravenous iron dextran”, 1964, Blood, 23, 354-58. Cerca con Google

Master A, Livingston M, Gupta AS, “Photodynamic nanomedicine in the treatment of solid tumours: perspectives and challenge”, 2013, J Control. Release, http://dx.doi.org./10.1016/j.jconrel.2013.02.020. Vai! Cerca con Google

Mazzola L, “Commercializing nanotechnology”, 2003, Nat Biotechnol, 21, 1137-1143. Cerca con Google

Mitra S, Foster TH, “Photophysical parameters, photosensitizer retention and tissue optical properties completely account for the higher photodynamic efficacy of meso-Tetra-Hydroxyphenyl-Chlorin vs Photofrin”, 2005, Photochem Photobiol, 81, 849-859. Cerca con Google

Mlkvy P, Messmann H, Regula J, Conio M, Pauer M, Millson CE, MacRobert AJ, Bown SG, “Photodynamic therapy for gastrointestinal tumors using three photosensitizers-ALA induced PPIX, Photofrin and MTHPC. A pilot study”, 1998, Neoplasma, 45, 157-161. Cerca con Google

Moghimi SM, “Opsono-recognition of liposomes by tissue macrophages”, 1998, Int J Pharmaceut, 162, 11–18. Cerca con Google

Moghimi SM, Patel HM, “Serum-mediated recognition of liposomes by phagocytic cells of the reticuloendothelial system - The concept of tissue specificity”, 1998, Adv Drug Deliver Rev, 32, 45–60. Cerca con Google

Moghimi SM, Hunter AC, Murray JC, “Long-circulating and target-specific nanoparticles: theory to practice”, 2001, Pharmacol Rev, 53, 283-318. Cerca con Google

Moghimi SM, Szebeni J, “Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties”, 2003, Prog Lipid Res, 42, 463-478. Cerca con Google

Namiki Y, Fuchigami T, Tada N, Kawamura R, Matsunuma S, Kitamoto Y, Nakagawa M, “Nanomedicine for cancer: lipid-based nanostructures for drug delivery and monitoring”, 2011, Accounts Chem Res, 44, 1080-1093. Cerca con Google

Nel A, Xia T, Madler L, Li N, “Toxic potential of materials at the nanolevel”, 2006, Science, 311, 622-627. Cerca con Google

Nyman ES, Hynninen PH, “Research advances in the use of tetrapyrrolic photosensitizers for photodynamic therapy”, 2004, J Photochem Photobiol B, 73, 1-28. Cerca con Google

Norman ME, Williams P, Illum L, “Human serum-albumin as a probe for surface conditioning (opsonization) of block copolymer-coated microspheres”, 1992, Biomaterials, 13, 841-849. Cerca con Google

O’Brien ME, Wigler N, Inbar M, Rosso R, Grischke E, Santoro A, Catane R, Kieback DG, Tomczak P, Ackland SP, Orlandi F, Mellars L, Alland L, Tendler C, “Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer”, 2004, Ann Oncol, 15, 440-449. Cerca con Google

Oberdörster G, Oberdörster E, Oberdörster J, “Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles”, 2005, Environ Health Persp, 113, 823-839. Cerca con Google

Oenbrink G, Jürgenlimke P, Gabel D, “Accumulation of porphyrins in cells: influence of hydrophobicity aggregation and protein binding”, 1988, Photochem Photobiol, 48, 451–456. Cerca con Google

Ohulchanskyy TY, Roy I, Goswami LN, Chen Y, Bergey EJ, Pandey RK, Oseroff AR, Prasad PN, “Organically modified silica nanoparticles with covalently incorporated photosensitizer for photodynamic therapy of cancer”, 2007, Nano Lett, 7, 2835-2842. Cerca con Google

Oleinick N, Morris R, Belichenko I, “The role of apoptosis in response to photodynamic therapy: What, where, why and how”, 2002, Photochem Photobiol Sci, 1, 1-21. Cerca con Google

Osseo-Asare K, Arriagada FJ, “Growth kinetics of nanosize silica in a nonionic water-in-oil microemulsion: a reverse micellar pseudophase reaction model”, 1999, J Colloid Interface Sci, 218, 68-76. Cerca con Google

Owens III DE, Peppas NA, “Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles”, 2006, Int J Pharmaceut, 307, 93-103. Cerca con Google

Pan X, Lee RJ, “Tumour-selective drug delivery via folate receptor-targeted liposomes”, 2004, Expert Opin Drug Deliv, 1, 7–17. Cerca con Google

Pantarotto D, Singh R, McCarthy D, Erhardt M, Briand JP, Prato M, Kostarelos K, Bianco A, “Functionalized carbon nanotubes for plasmid DNA delivery”, 2004, Angew Chem Int Ed Engl, 43, 5242-5246. Cerca con Google

Park W, Hong K, Kirpotin DB, Colbern G, Shalaby R, Baselga J, Shao Y, Nielsen UB, Marks JD, Moore D, Papahadjopoulos D, Benz CC, “Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery”, 2002, Clin Cancer Res, 8, 1172–1181. Cerca con Google

Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R, “Nanocarriers as an emerging platform for cancer therapy”, 2007, Nat Nanotechnol, 2, 751-760. Cerca con Google

Pegaz B, Debefve E, Ballini JP, Wagnieres G, Spaniol S, Albrecht V, Scheglmann DV, Nifantiev NE, Van der Bergh H, Konan-Kouakou YN, “Photothrombic activity of m-THPC-loaded liposomal formulations: pre-clinical assessment on chick chorioallantonic membrane model”, 2006, Eur J Pharm Sci, 28, 134–140. Cerca con Google

Peng CL, Yang LY, Luo TY, Lai PS, Yang SJ, Lin WJ, Shieh MJ, “Development of pH sensitive 2-(diisopropylamino)ethyl methacrylate based nanoparticles for photodynamic therapy”, 2010, Nanotechnology, 21, 155103. Cerca con Google

Prahabaran M, Grailer JJ, Pilla S, Steeber DA, Gong S, “Gold nanoparticles with a monolayer of doxorubicin-conjugated amphiphilic block copolymer for tumour targeted drug delivery”, 2009, Biomaterials, 30, 6065-6075. Cerca con Google

Polo L, Valduga G, Jori G, Reddi E, “Low-density lipoprotein receptors in the uptake of tumour photosensitizers by human and rat transformed fibroblasts”, 2002, Int J Biochem Cell B, 34, 10-22. Cerca con Google

Popovic Z, Liu W, Chauan VP, Lee J, Wong C, Greytak AB, Insin N, Nocera DG, Fukumura D, Jain RK, Bawendi MG, “A nanoparticle size series for in vivo fluorescence imaging”, 2010, Angew Chem Int Ed Engl, 49, 8649-8652. Cerca con Google

Reddy GR, Bhojani MS, McConville P, Moody J, Moffat BA, Hall DE, Kim G, Koo YE, Woolliscroft MJ, Sugai JV, Johnson TD, Philbert MA, Kopelman R, Rehemtulla A, Ross BD, “Vascular targeted nanoparticles for imaging and treatment of brain tumors”, 2006, Clin Cancer Res, 12, 6677-6686. Cerca con Google

Remaut K, Lucas B, Braeckmans K, Demeester J, de Smed SC, “Pegylation of liposomes favours the endosomal degradation of the delivered phosphodiester oligonucleotides”, 2007, J Control Release, 117, 256–266. Cerca con Google

Reshetov V, Kachatkou D, Shmigol T, Zorin V, D’Hallewin M, Guillemin F, Bezdetnaya L, “Redistribution of meta-tetra(hydroxyphenyl)chlorin (m-THPC) from conventional and PEGylated liposomes to biological substrates”, 2011, Photochem Photobiol Sci, 10, 911–919. Cerca con Google

Ricci-Júnior E, Marchetti JM “Preparation, characterization, photocytotoxicity assay of PLGA nanoparticles containing zinc (II) phthalocyanine for photodynamic therapy use”, 2006, J Microencapsul, 5, 523-538. Cerca con Google

Rio-Echevarria IM, Selvestrel F, Segat D, Guarino G, Tavano R, Causin V, Reddi E, Papini M, Mancin F, “Highly PEGylated silica nanoparticles: “ready to use” stealth functional nanocarriers”, 2010, J Mater Chem, 20, 2780-2787. Cerca con Google

Roco MC, “Broader societal issues of nanotechnology”, J Nanopart Res, 2003, 5, 181-189. Cerca con Google

Romberg B, Hennink WE, Storm G, “Sheddable coatings for long-circulating nanoparticles”, 2008, Pharm Res, 25, 55-71. Cerca con Google

Roser M, Fischer D, Kissel T, “Surface-modified biodegradable albumin nano- and microspheres. II. Effect of surface charges on in vitro phagocytosis and biodistribution in rats”, 1998, Eur J Pharm Biopharm, 46, 255-263. Cerca con Google

Roy I, Ohulchanskyy TY, Pudavar HE, Bergey EH, Oseroff AR, Morgan J, Dougherty TJ, Prasad PN, “Ceramic-based nanoparticles entrapping water-insoluble photosensitizing anticancer drug. A novel drug-carrier system for photodynamic therapy”, 2003, J A Chem Soc, 125, 7860-7865. Cerca con Google

Roy I, Ohulchanskyy TY, Bharali DJ, Pudavar HE, Mistretta RA, Kaur N, Prasad PN, “Optical tracking of organically modified silica nanoparticles as DNA carriers: A nonviral, nanomedicine approach for gene delivery”, 2005, Proc Natl Acad Sci USA, 102, 279-284. Cerca con Google

Sasnouski S, Zorin V, Khludeyev I, D’Hallewin MA, Guillemin F, Bezdetnaya L, “Investigation of Foscan® interactions with plasma proteins”, 2005, Biochim Biophys Acta, 1725, 394-402. Cerca con Google

Senge MO, Brandt JC, “Temoporfin (Foscan®, 5,10,15,20-Tetra(m-hydroxyphenyl)chlorin)- A second-generation Photosensitizer”, 2011, Photochem Photobiol, 87, 1240–1296. Cerca con Google

Schiffelers RM, Koning GA, ten Hagen TLM, Fensa MHAM, Schraac AJ, Janssena APCA, Kokd RJ, Molemac G, Storm G, “Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin”, 2003, J Control Release, 91, 115–122. Cerca con Google

Shenoy D, Fu W, Li J, Crasto C, Jones G, Di Marzio C, Sridhar S, Amiji M, “Surface functionalisation of gold nanoparticles using hetero-bifunctional poly(ethylene glycol) spacer for intracellular tracking and delivery”, 2006, Int J Nanomedicine, 1, 51-57. Cerca con Google

Shieh MJ, Peng CL, Chiang WL, Wang CH, Hsu CY, Wang SJ, Lai PS, “Reduced skin photosensitivity with meta-tetra(hydroxyphenyl)chlorin loaded micelles based on a poly(2-ethyl-2-oxazoline)-bpoly(D,L-lactide) diblock copolymer in vivo”, 2010, Mol Pharm, 7, 1244–1253. Cerca con Google

Shen H, Sun T, Ferrari M, “Nanovector delivery of siRNA for cancer therapy”, 2012, Cancer Gene Therapy, 19, 367-373. Cerca con Google

Shmeeda H, Tzemach D, Mak L, Gabizon A, “Her2-targeted pegylated liposomal doxorubicin: retention of target-specific binding and cytotoxicity after in vivo passage”, 2009, J Control Rel, 136, 155–160. Cerca con Google

Shvedova AA, Kisin ER, Mercer R, Murray AR, Johnson VJ, Potapovich AI, Tyurina YY, Gorelik O, Arepalli S, Schwegler-Berry D, Hubbs AF, Antonini J, Evans DE, Ku BK, Ramsey D, Maynard A, Kagan VE, Castranova V, Baron P, “Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice”, 2005, Am J Physiol, 289, L698-708. Cerca con Google

Silverstein SB, Rodgers GM, “Parental iron therapy options”, 2004, Am J Hematol, 76, 74-78. Cerca con Google

Stöber W, Fink A, Bohn E, “Controlled growth of monodisperse silica spheres in the micron size range”, 1968, J Colloid Interface Sci, 26, 68-76. Cerca con Google

Sumer B, Gao J, “Theranostic nanomedicine for cancer”, 2008, Nanomedicine, 3, 137-140. Cerca con Google

Sun D, “Nanotheranostics: integration of imaging and targeted drug delivery”, 2010, Mol Pharm, 7, 1879. Cerca con Google

Svensson, J, Johannson A, Bendsoe N, Gräfe S, Trebst T, Andersson-Engels S, Svanberg K, “Pharmacokinetic study of a systemically administered novel liposomal Temoporfin formulation in an animal tumor model”, 2007, Proc SPIE Int Soc Opt Eng, 6427, 64270T. Cerca con Google

Svensson J, Johansson A, Gräfe, Gitter B, Trebst T, Bendsoe N, Andersson-Engels S, Svanberg K, “Tumor selectivity at short times following systemic administration of a liposomal temoporfin formulation in a murine tumor model”, 2007, Photochem Photobiol, 83, 1211–1219. Cerca con Google

Svenson S, “Dendrimers as versatile platform in drug delivery applications”, 2009, Eur J Pharm Biopharm, 71, 445-462. Cerca con Google

Syu WJ, Yu HP, Hsu CY, Rajan YC, Hsu YH, Chang YC, Hsieh WY, Wang CH, Lai PS, “Improved photodynamic cancer treatment by folate conjugated polymeric micelles in a KB xenografted animal model”, 2012, Small, 13, 2060–2069. Cerca con Google

Takhar P, Mahant S, “In vitro methods for nanotoxicity assessment: advantages and applications”, 2011, Arch Appl Sci Res, 3, 389-403. Cerca con Google

Torchilin VP, “Drug targeting”, 2000, Eur J Pharm Sci, 11 (Suppl. 2), S81-91. Cerca con Google

Torchilin VP, “Multifunctional nanocarriers”, 2006, Adv Drug Deliver Rev, 58, 1532-1555. Cerca con Google

Uehlinger P, Zellweger M, Wagnieres G, Juillerat-Jeanneret L, van der Bergh H, Lange N, “Aminolevulinic acid and its derivatives: physical chemical properties and protoporphyrin IX formation in cultured cells”, 2000, J Photochem Photobiol B, 54, 72-80. Cerca con Google

Unfried K, Albrecht C, Klotz LO, Von Mikecz A, Grether-Beck S, Schins RPF, “Cellular responses to nanoparticles: Target structures and mechanisms”, 2007, Nanotoxicology, 1, 52-71. Cerca con Google

Valencia PM, Hanewich-Hollatz MH, Gao W, Karima F, Langer R, Karnik R, Farokhzad OC, “Effects of ligands with different water solubilities on self-assembly and properties of targeted nanoparticles”, 2011, Biomaterials, 32, 6226-6233. Cerca con Google

Van Geel IP, Oppelaar H, Oussoren YG, van der Valk MA, Stewart FA, “Photosensitizing efficacy of MTHPC-PDT compared to Photofrin-PDT in the RIFl mouse tumour and normal skin”, 1995, Int J Cancer, 60, 388-394. Cerca con Google

Van Vlerken LE, Amiji MM, “Multi-functional polymeric nanoparticles for tumour-targeted drug delivery”, 2006, Expert Opinion on Drug Delivery, 3, 205-216. Cerca con Google

Vargas A, Lange N, Arvinte T, Cerny R, Gurny R, Delie F, “Toward the understanding of the photodynamic activity of m-THPP encapsulated in PLGA nanoparticles: correlation between nanoparticle properties and in vivo activity”, 2009, J Drug Target, 17, 599-609. Cerca con Google

Vega-Villa KR, Takemoto JK, Yáñez JA, Remsberg CM, Forrest ML, Davies NM, “Clinical toxicities of nanocarrier systems”, 2008, Adv Drug Deliver Rev, 60, 929-938. Cerca con Google

Vert M, Mauduit J, Li S, “Biodegradation of PLA/GA polymers: increasing complexity”, 1994, Biomaterials, 15, 1209-1213. Cerca con Google

Wacker M, Chen K, Preuss A, Possemeyer K, Röder B, Langer K, “Photosensitizer loaded HSA nanoparticles. I: Preparation and photophysical properties”, 2010, Int J Pharmaceut, 393, 253–262. Cerca con Google

Wang X, Wang Y, Chen ZG, Shin DM, “Advances of cancer therapy by nanotechnology”, 2009, Cancer Res Treat, 41, 1-11. Cerca con Google

Wang M, Thanou M, “Targeting nanoparticles to cancer”, 2010, Pharmacol Res, 62, 90-99. Cerca con Google

Warner S, “Diagnostics plus therapy = theranostics”, 2004, Scientist, 18, 38-39. Cerca con Google

Weeldon I, Farhadi A, Bick AG, Jabbari E, Khademhosseini A, “Nanoscale tissue engineering: spatial control over cell-materials interactions”, 2011, Nanotechnology, 22, 212001. Cerca con Google

Weetall HH, “Storage stability of water-insoluble enzymes covalently coupled to organic and inorganic carriers”, 1970, Biochim Biophys Acta, 212, 1-7. Cerca con Google

Yang L, Peng XH, YA Wang, Wang X, Cao Z, Ni C, Karna P, Zhang X, Wood WC, Gao X, Nie S, Mao H, “Receptor-targeted nanoparticles for in vivo imaging of breast cancer”, 2009, Clin Cancer Res, 15, 4722–4732. Cerca con Google

Yamaoka T, Tabata T, Ikada Y, “Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice”, 1994, J Pharm Sci, 83, 601-606. Cerca con Google

Yan F, Kopelman R, “The embedding of metatetra(hydroxyphenyl)-chlorin into silica nanoparticle platforms for photodynamic therapy and their singlet oxygen production and pH-dependent optical properties”, 2003, Photochem Photobiol, 78, 587–591. Cerca con Google

Yan X, Kuipers F, Havekes LM, Havinga R, Dontje B, Poelstra K, Scherpof GL, Kamps JA, “The role of Apolipoprotein E in the elimination of liposomes from blood by hepatocytes in the mouse”, 2005, Biochem Biophys Res Commun, 328, 57-62. Cerca con Google

Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, Atwal J, Elliott JM, Prabhu S, Watts RJ, Dennis MS, “Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target”, 2011, Sci Transl Med, 3, 84ra44. Cerca con Google

Yu MK, Park J, Jon S, “Targeting strategies for multifunctional nanoparticles in cancer imaging and therapy”, 2012, Theranostics, 2, 3-44. Cerca con Google

Zalipsky S, “Chemistry of polyethylene glycol conjugates with biologically active molecules”, 1995, Adv Drug Deliv Rev, 16, 157-182. Cerca con Google

Zhang M, Murakami T, Ajima K, tsuchida K, Sandanayaka ASD, Ito O, Iijima S, Yudasaka M, “Fabrication of ZnPc/protein nanohorns for double photodynamic and hyperthermic cancer phototherapy”, 2008, Proc Natl Acad Sci USA, 105, 14773-14778. Cerca con Google

Zeisser-Labouèbe M, Vargas A, Delie F, “Nanoparticles for photodynamic therapy of cancer”, 2006, C.S. Kumar (Ed.), Nanomaterials for Cancer Therapy, Vol. 6 Wiley-VCH, Weinheim, pp. 40–86. Cerca con Google

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