title: Smart pH/Redox Dual-Responsive Nanogels for On-Demand Intracellular Anticancer Drug Release.
abstract: Efficient accumulation and intracellular drug release in cancer cells remain a crucial challenge in developing ideal anticancer drug delivery systems. Here, poly(N-isopropylacrylamide)-ss-acrylic acid (P(NIPAM-ss-AA)) nanogels based on NIPAM and AA cross-linked by N,N'-bis(acryloyl)cystamine (BAC) were constructed by precipitation polymerization. The nanogels exhibited pH/redox dual responsive doxorubicin (DOX) release behavior in vitro and in tumor cells, in which DOX release from nanogels was accelerated in lysosomal pH (pH 4.5) and cytosolic reduction (10 mM GSH) conditions. Moreover, intracellular tracking of DOX-loaded nanogels confirmed that after the nanogels and the loaded DOX entered the cells simultaneously mainly via lipid raft/caveolae-mediated endocytosis, DOX-loaded nanogels were transported to lysosomes and then the loaded DOX was released to nucleus triggered by lysosomal pH and cytoplasmic high GSH. MTT analysis showed that DOX-loaded nanogels could efficiently inhibit the proliferation of HepG2 cells. In vivo animal studies demonstrated that DOX-loaded nanogels were accumulated and penetrated in tumor tissues more efficiently than free DOX. Meanwhile, DOX-loaded nanogels exhibited stronger tumor inhibition activity and fewer side effects. This study indicated that pH/redox dual-responsive nanogels might present a prospective platform for intracellular drug controlled release in cancer therapy.
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, and §School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, and §School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, and §School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, and §School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Xiao
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, and §School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
authors.forename: Fuying
authors.initials: F
authors.lastname: Li
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, and §School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, and §School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology , Wuhan 430074, China.
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004317:Doxorubicin
keywords: cancer therapy; controlled drug release; nanogels; pH/redox dual responsiveness; tumor accumulation and penetration