Pop silica · Towards Biodegradable Nanoparticles: Hybrid Organic Mesoporous Silica

Towards Biodegradable Nanoparticles: Hybrid Organic Mesoporous Silica

“Pop goes the particle”: the incorporation of physiologically responsive functional groups in the framework of mesoporous silica nanoparticles (NPs) is expected to beneficially affect the therapeutic performance of this material, by fostering an enhanced drug-release activity as well as an exhaustive biodegradation. Indeed, the issue of complete and safe excretion of NPs from the biological system after accomplishing their diagnostic or therapeutic functions has not yet been entirely addressed, remaining one of the major obstacles impeding their potential clinical translation as nano-medical tools. Following this approach, thanks to the MSC-funded project POP SILICA, we were able to develop a novel mesoporous organo-silica nanoparticle containing redox responsive disulfide (S-S) bridges (ss-NPs) directly inserted in its framework that, in the presence of reducing agents, undergo degradation enhancing the local release activity of the particle. This material, still preserving all the valuable characteristics of the inorganic particle (porosity, bio-compatibility, possibility of orthogonal functionalization, etc.), resulted to be endowed with a greater tendency to release its cargo and degrade when in presence the favourable reducing stimulus. More importantly, these peculiar properties were also confirmed within cancer cells. The superior disintegration ability of ss-NPs was in fact investigated upon incubation in Glioma C6 cancer cells, where our bio-responsive hybrid was not only found to be uptaken to a higher extent in comparison to NPs, but also able to better deliver drugs and to be more rapidly excreted. Indeed, when anticancer drug temozolomide (TMZ)-loaded ss-NPs were fed to Glioma C6 cells, the responsive hybrid resulted more effective in its cytotoxic action compared to non-breakable particles, thanks again to the rippening of the disulfide bridges present in the framework of the particle. Moreover, it was demonstrated that the responsive self-destructive behaviour of ss-NPs could be also preserved upon surface functionalization with biologically relevant targeting ligands (i.e. folic acid, RGD peptide, Erbitux® antibody). This targeting could then assure the possibility of employing this hybrid material in active cancer-targeting strategies without losing its enhanced delivery and excretion performances. Preliminary in vivo investigations reveal the biocompatibilty of ss-NPs, which did cause any toxicity in the animal models to which they were administered. For this reason, further study is on-going with anticancer drug doxorubicine loaded ss-NPs directly injected inside tumor models, to evaluate the effect of the breakable bonds on the drug delivery ability in vivo of mesoporous silica nanoparticles. In conclusions, due to its outstanding cellular internalization and release kinetics, this system may pave the way towards a more efficient employment of silica-based nanovectors in nanotheranostic applications. The next challenge to address regards the transition of this technology in vivo. Optimization of the surface functionalization, complete toxicological study, and assay of the drug delivery performance of ss-NPs in vivo, are now to be considered the next key points to be attended, towards their implementation in regular therapeutic applications.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз