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Open AccessArticle

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

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Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo, Viale delle Scienze, Edificio 16, 90128 Palermo, Italy
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Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 6, 90128 Palermo, Italy
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Consiglio Nazionale delle Ricerche (CNR)—Istituto di Biofisica (IBF) UOS Palermo, Via U. La Malfa 153, 90146 Palermo, Italy
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Consiglio Nazionale delle Ricerche (CNR)—Istituto per lo Studio dei Materiali Nanostrutturati (ISMN) UOS Palermo, Via Ugo La Malfa, 153, 90146 Palermo, Italy
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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
Molecules 2016, 21(11), 1594; https://doi.org/10.3390/molecules21111594
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)
(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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