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- W2741099343 abstract "Long circulation in blood, enhanced tumor accumulation and penetration, efficient cellular internalization and intracellular drug release are major challenges in the development of ideal anticancer drug delivery systems. Although several strategies have been reported to improve therapeutic efficacy, they mainly meet one or a few features which can not circumvent all the barriers. Here the stimuli-responsive zwitterionic nanogels were developed to overcome the sequential physiological barriers in cancer chemotherapy. The nanogels were constructed via a simple precipitation polymerization method by using temperature-sensitive monomer N-isopropylacrylamide (NIPAM) pH-responsive monomer methylallyl amine (MAA) and betaine-based zwitterionic monomer sulfobetaine methacrylate (SBMA) with in vivo anti-protein adsorption property as comonomers, and disulfide bonds-containing N, N9-bis(acryloyl) cystamine (BAC) as crosslinker. Volume phase transition temperature (VPTT) and surface charge of the prepared nanogels were precisely controlled by altering the feeding molar ratio of these comonomers. Remarkably, The nanogels possess ultra-pH sensitive hydrophilicity/hydrophobicity reversible property, in which the nanogels were hydrophilic in the blood (pH 7.4, 37 °C) for prolonged circulation, while they were rapidly switched to hydrophobic with similar size and surface charge at acidic tumor pH, resulting in enhanced tumor accumulation and penetration and strong internalization by normal cancer cells and CSCs. For efficient lysosomal escape and intracellular drug release, the nanogels were positively charged at lysosome pH, which allowed them to be transported into the cytosol where the loaded cargo DOX was released from the nanogels with the introduction of intracellular high GSH concentration to exert cytotoxicity. This study indicated that pH-dependent hydrophilicity/hydrophobicity-, surface charge-reversible and redox sensitive nanogels might be used as potential carriers for anticancer drugs, which provided a foundation for designing an effective drug delivery system for cancer therapy. Note: This abstract was not presented at the meeting. Citation Format: Hao Yang, Qin Wang, Fuying Li, Yanhong Zhu, Lu Gan, Xiangliang Yang. pH-regulated hydrophilicity/hydrophobicity-, surface charge-reversible and redox sensitive nanogels for anticancer drug delivery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3099. doi:10.1158/1538-7445.AM2017-3099" @default.
- W2741099343 created "2017-08-08" @default.
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- W2741099343 date "2017-07-01" @default.
- W2741099343 modified "2023-09-26" @default.
- W2741099343 title "Abstract 3099: pH-regulated hydrophilicity/hydrophobicity-, surface charge-reversible and redox sensitive nanogels for anticancer drug delivery" @default.
- W2741099343 doi "https://doi.org/10.1158/1538-7445.am2017-3099" @default.
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