title: Targeted delivery of photosensitizers: efficacy and selectivity issues revealed by multifunctional ORMOSIL nanovectors in cellular systems.
abstract: PEGylated and non-PEGylated ORMOSIL nanoparticles prepared by microemulsion condensation of vinyltriethoxy-silane (VTES) were investigated in detail for their micro-structure and ability to deliver photoactive agents. With respect to pure silica nanoparticles, organic modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophysical properties of embedded photosensitizers and the interaction of the nanoparticles with biological entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid preparation and screening of multifunctional nanosystems for photodynamic therapy (PDT). Selective targeting of model cancer cells was tested by using folate, an integrin specific RGD peptide and anti-EGFR antibodies. Data suggest the interference of the stealth-conferring layer (PEG) with small targeting agents, but not with bulky antibodies. Moreover, we showed that selective photokilling of tumour cells may be limited even in the case of efficient targeting because of intrinsic transport limitations of active cellular uptake mechanisms or suboptimum localization.
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Padova, via Marzolo 1, Padova I-35131, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Selvestrel
authors.forename: Francesca
authors.initials: F
authors.lastname: Moret
authors.forename: Daniela
authors.initials: D
authors.lastname: Segat
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Woodhams
authors.forename: Giulio
authors.initials: G
authors.lastname: Fracasso
authors.forename: Iria M Rio
authors.initials: IM
authors.lastname: Echevarria
authors.forename: Luca
authors.initials: L
authors.lastname: Baù
authors.forename: Federico
authors.initials: F
authors.lastname: Rastrelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Compagnin
authors.forename: Elena
authors.initials: E
authors.lastname: Reddi
authors.forename: Chiara
authors.initials: C
authors.lastname: Fedeli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Papini
authors.forename: Regina
authors.initials: R
authors.lastname: Tavano
authors.forename: Alexandra
authors.initials: A
authors.lastname: MacKenzie
authors.forename: Melissa
authors.initials: M
authors.lastname: Bovis
authors.forename: Elnaz
authors.initials: E
authors.lastname: Yaghini
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: MacRobert
authors.forename: Silvia
authors.initials: S
authors.lastname: Zanini
authors.forename: Anita
authors.initials: A
authors.lastname: Boscaini
authors.forename: Marco
authors.initials: M
authors.lastname: Colombatti
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Mancin
mesh_terms: D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D012833:Siloxanes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000912:Antibodies, Neoplasm; D009842:Oligopeptides; D017319:Photosensitizing Agents; D012833:Siloxanes; C510784:ormosil; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; C512478:EGFR protein, human; D066246:ErbB Receptors