Multistimuli-Responsive PEGylated Polymeric Bioconjugate-Based Nano-aggregate for Cancer Therapy

Publication date: Available online 19 November 2019Source: Chemical Engineering JournalAuthor(s): Kai Chen, Shuangsi Liao, Shiwei Guo, Xiuli Zheng, Bing Wang, Zhenyu Duan, Hu Zhang, Qiyong Gong, Kui LuoAbstractBiocompatible, stimuli-responsive, intelligent and efficient drug delivery systems are essential for effectively suppressing cancer and reducing toxic side effects of chemotherapeutic drugs. Herein, two strategies have been employed to develop a N-(1,3-dihydroxypropan-2-yl) methacrylamide (DHPMA)-derived polymer carrier for doxorubicin (DOX) with a long circulation time: increasing molecular weight (MW) of the DHPMA polymer through an enzyme-responsive oligopeptide linker; and further grafting poly(ethylene glycol) (PEG) onto the polymer chain via a disulfide bond (pDHPMA-DOX-SS-mPEG), resulting in nano-aggregate. The nano-aggregate enters into 4T1 cells through multiple endocytosis pathways and DOX released in the presence of a low pH and reductive enzymes contributes to significant apoptosis by decreasing mitochondria membrane potential and disrupting actin cytoskeletons. Significantly enhanced tumor accumulation of the nano-aggregate is evidenced from ex vivo fluorescence imaging in comparison with the bioconjugate (pDHPMA-DOX) with no PEGylation. This is supported with a much longer terminal half-life time up to 16.9 h for pDHPMA-DOX-SS-mPEG, significantly higher than 10.4 h for pDHPMA-DOX and 2.7 h for free drug DOX. Accordingly, the best tumor inhibitive effect ha...
Source: Chemical Engineering Journal - Category: Chemistry Source Type: research

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