Multi-functional nanogels for tumor targeting and redox sensitive drug and siRNA delivery

Background: A new family of nanosystems able to discern between normal and tumor cells and to release therapeutic agent in controlled way, were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs). (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a glutathione sensitive spacer, in order to obtain a controlled release mechanism, specific for cancer cells. The drug efficiency was tested on tumor and healthy cells by flow cytometric analysis, confocal and epifluorescence microscopy and cytotoxicity assay; while the siRNA effect was investigated by RNAi experiment. (3) Results: The data obtained showed that the use of NGs permits a faster cargo release in cancer cells, in response to high cytosolic glutathione level, improving also their efficacy. (4) Conclusion: Thus, the possibility to release biological molecules in controlled way and to recognize a specific tumor target, allow to overcome the typical limits of the classic cancer therapy.