title: Dual temperature/pH-sensitive drug delivery of poly(N-isopropylacrylamide-co-acrylic acid) nanogels conjugated with doxorubicin for potential application in tumor hyperthermia therapy.
abstract: In this paper, a dual temperature/pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) nanogel (PNA) was prepared and utilized as a drug carrier. The anti-cancer drug doxorubicin (DOX) was covalent bound to PNA via an acid-labile hydrazone linkage. DOX-PNA conjugates had a pH-dependent LCST, which was 41°C and 43°C at pH 5.3 and 6.8 respectively, but higher than 50°C at pH 7.4. The nanogels which were hydrophilic below LCST and changed to hydrophobic state above LCST possessed dual pH/temperature dependent cellular uptake and cytotoxicity. With increasing temperature, the cellular uptake of DOX-PNA was almost no difference at pH 7.4, but enhanced about 43% at pH 6.8. So the cytotoxicity of DOX-PNA also increased in higher temperature and lower pH value. It was able to distinguish tumor extracellular pH from physiological pH under hyperthermia of 43°C, suggesting a great potential for anti-cancer therapy.
authors.affiliation: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huabing
authors.initials: H
authors.lastname: Chen
authors.forename: Huibi
authors.initials: H
authors.lastname: Xu
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D013696:Temperature
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine; C067295:N-isopropylacrylamide