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Molecules 2016, 21(11), 1594;

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

Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo, Viale delle Scienze, Edificio 16, 90128 Palermo, Italy
Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 6, 90128 Palermo, Italy
Consiglio Nazionale delle Ricerche (CNR)—Istituto di Biofisica (IBF) UOS Palermo, Via U. La Malfa 153, 90146 Palermo, Italy
Consiglio Nazionale delle Ricerche (CNR)—Istituto per lo Studio dei Materiali Nanostrutturati (ISMN) UOS Palermo, Via Ugo La Malfa, 153, 90146 Palermo, Italy
Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742, USA
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 4 August 2016 / Revised: 18 October 2016 / Accepted: 16 November 2016 / Published: 23 November 2016
(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)
Full-Text   |   PDF [8019 KB, uploaded 23 November 2016]   |  


(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. View Full-Text
Keywords: PVP; nanogels; e-beam; folate-targeting; doxorubicin; siRNA; GSH-responsive release PVP; nanogels; e-beam; folate-targeting; doxorubicin; siRNA; GSH-responsive release

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Adamo, G.; Grimaldi, N.; Campora, S.; Bulone, D.; Bondì, M.L.; Al-Sheikhly, M.; Sabatino, M.A.; Dispenza, C.; Ghersi, G. Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery. Molecules 2016, 21, 1594.

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