Final Report Summary - POP SILICA (Towards Biodegradable Nanoparticles: Hybrid Organic Mesoporous Silica)
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.