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.

Multifunctional organically modified silica nanoparticles for chemotherapy, adjuvant hyperthermia and near infrared imaging

“…This indicates a possible porous structure. 15,16 Sharp peaks at 1407 cm −1 and 1605 cm −1 indicate in plane CH 2 bending and C=C vibrations from the vinyl groups. Furthermore, the peaks at 2969 cm −1 (aliphatic H-C), 3074 cm −1 (aromatic H-C) and at 3400 cm −1 (N-H, O-H) are due to the functional groups on the surface.…”

Silicon-containing nanocarriers for targeted drug delivery: synthesis, physicochemical properties and acute toxicity

“…Therefore, there is great interest surrounding organomodified silica NPs, which combine the properties of organic and inorganic substances. OrSiO 2 NPs have recently emerged as an attractive candidate for nanomedical applications (Selvestrel et al, 2013). Methods of OrSiO 2 NPs synthesis are well characterized (Roy et al, 2012).…”

“…Several studies have explored the methods of cancer photodynamic therapy using OrSiO 2 NP-embedded photosensitizers (Selvestrel et al, 2013;Singh et al, 2014). Another important application of OrSiO 2 NPs is the targeted delivery of genetic constructs into the cell (Bharali et al, 2005).…”

Parallel optical read-out of micromechanical pillars applied to prostate specific membrane antigen detection

“…In order to functionalize the pillar sensor against PSMA: i) a layer of Au was evaporated on the pillar top layer immediately before the functionalization procedure; ii) a monoclonal antibody anti-PSMA (D2B) (Colombatti et al 2010) was functionalized with a thiol group (Selvestrel et al 2013) to be linked to the Au surface; iii) the chips were incubated for 10 minutes at room temperature in 20 L of D2B solution at 70nM in a vapor saturated environment to avoid droplet drying; iv) the chips were rinsed in PBS, blown dried in N 2 . and used for PSMA detection.…”