title: Charge-conversional and reduction-sensitive poly(vinyl alcohol) nanogels for enhanced cell uptake and efficient intracellular doxorubicin release.
abstract: Charge-conversional and reduction-sensitive polyvinyl alcohol (PVA) nanogels were developed for efficient cancer treatment by enhanced cell uptake and intracellular triggered doxorubicin (DOX) release. These PVA nanogels were prepared in a straightforward manner by inverse nanoprecipitation via "click" reaction with an average diameter of 118nm. The introduction of COOH into the PVA nanogels efficiently improved the DOX encapsulation due to the electrostatic interaction. The in vitro release result showed that the decrease of electrostatic interaction between COOH and DOX under a mimicking endosomal pH, in combination with the cleavage of the intervening disulfide bonds in response to a high glutathione (GSH) concentration led to a fast and complete release of DOX. Furthermore, confocal laser scanning microscopy (CLSM) revealed that the ultra pH-sensitive terminal groups allowed nanogels to reverse their surface charge from negative to positive under a tumor extracellular pH (6.5-6.8) which facilitated cell internalization. MTT assays and real time cell analysis (RTCA) showed that these DOX-loaded charge-conversional and reducible PVA nanogels had much better cell toxicity than DOX-loaded non-charge-conversional or reduction-insensitive PVA nanogels following 48h of incubation. These novel charge-conversional and stimuli-responsive PVA nanogels are highly promising for targeted intracellular anticancer drug release.
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Achazi
authors.affiliation: Research Center of Electron Microscopy, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Fabeckstrasse 36a, Berlin 14195, Germany.
authors.forename: Boris
authors.initials: B
authors.lastname: Schade
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany. Electronic address: haag@chemie.fu-berlin.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D057930:Click Chemistry; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004337:Drug Carriers; D005260:Female; D005782:Gels; D006801:Humans; D006863:Hydrogen-Ion Concentration; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D018613:Microscopy, Confocal; D050997:Nanomedicine; D053758:Nanoparticles; D010084:Oxidation-Reduction; D010316:Particle Size; D011142:Polyvinyl Alcohol / Q000031:analogs & derivatives / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D004317:Doxorubicin; D011142:Polyvinyl Alcohol
keywords: Charge-conversion; Drug delivery; Inverse nanoprecipitation; PVA nanogel; Stimuli-responsive