Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery

Author： Adamo Giorgia Grimaldi Natascia Campora Simona Bulone Donatella Bondì Maria Luisa Al-Sheikhly Mohamad Sabatino Maria Antonietta Dispenza Clelia Ghersi Giulio

Publisher： MDPI

E-ISSN： 1420-3049|21|11|1594-1594

ISSN： 1420-3049

Source： Molecules, Vol.21, Iss.11, 2016-11, pp. : 1594-1594

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Abstract

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a 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 the 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; 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, also improving their efficacy; (4) Conclusion: The possibility of releasing biological molecules in a controlled way and to recognize a specific tumor target allows overcoming the typical limits of the classic cancer therapy.