Targeted delivery of photosensitizers: efficacy and selectivity issues revealed by multifunctional ORMOSIL nanovectors in cellular systems

PEGylated and non-PEGylated ORMOSIL nanoparticles prepd. 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, org. modification substantially changes the microstructure and the surface properties. This in turn leads to a modulation of both the photophys. properties of embedded photosensitizers and the interaction of the nanoparticles with biol. entities such as serum proteins. The flexibility of the synthetic procedure allows the rapid prepn. 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 tumor cells may be limited even in the case of efficient targeting because of intrinsic transport limitations of active cellular uptake mechanisms or suboptimum localization.