title: Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery.
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.
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo, Viale delle Scienze, Edificio 16, 90128 Palermo, Italy. giorgia.adamo@unipa.it.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Adamo
authors.affiliation: Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 6, 90128 Palermo, Italy. ngrimaldi@icmab.es.
authors.forename: Natascia
authors.initials: N
authors.lastname: Grimaldi
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo, Viale delle Scienze, Edificio 16, 90128 Palermo, Italy. simona.campora@unipa.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Campora
authors.affiliation: Consiglio Nazionale delle Ricerche (CNR)-Istituto di Biofisica (IBF) UOS Palermo, Via U. La Malfa 153, 90146 Palermo, Italy. donatella.bulone@pa.ibf.cnr.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Bulone
authors.affiliation: Consiglio Nazionale delle Ricerche (CNR)-Istituto per lo Studio dei Materiali Nanostrutturati (ISMN) UOS Palermo, Via Ugo La Malfa, 153, 90146 Palermo, Italy. bondi@pa.ismn.cnr.it.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Bondì
authors.affiliation: Department of Materials Science and Engineering, University of Maryland, College Park, MD 20742, USA. mohamad@umd.edu.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Al-Sheikhly
authors.affiliation: Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 6, 90128 Palermo, Italy. mariaantonietta.sabatino@unipa.it.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Sabatino
authors.affiliation: Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 6, 90128 Palermo, Italy. clelia.dispenza@unipa.it.
authors.forename: Clelia
authors.initials: C
authors.lastname: Dispenza
authors.affiliation: Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo, Viale delle Scienze, Edificio 16, 90128 Palermo, Italy. giulio.ghersi@unipa.it.
authors.forename: Giulio
authors.initials: G
authors.lastname: Ghersi
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism; D058972:Folic Acid Transporters / Q000037:antagonists & inhibitors; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D000080385:Nanogels; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry* / Q000494:pharmacology; D011205:Povidone / Q000737:chemistry / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D058972:Folic Acid Transporters; D000080385:Nanogels; D034741:RNA, Small Interfering; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine; D005492:Folic Acid; D011205:Povidone
keywords: GSH-responsive release; PVP; doxorubicin; e-beam; folate-targeting; nanogels; siRNA