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Engineered borate ester conjugated protein-polymer nanoconjugates for pH-responsive drug delivery

Abstract : To improve the clinical efficiency of cytotoxic anticancer drugs e.g. doxorubicin (DOX), reduce the severe off-target side effects, and allow the more biocompatible and biodegradable drug penetration into tumor cells, our research efforts developed a new DOX-conjugated protein polymer nanoconjugates (PPNCs) prodrugs delivery system. Briefly, DOX was conjugated to bovine serum albumin (BSA) and the complex was treated with lactobionic acid (LA) as well as folic acid (FA) to enhance drug endocytosis and targeting selectivity. Such functionalized BSA could be conjugated with a designed phenylboronic acid functionalized poly(N-isopropylacrylamide) (PNIPAAm) via forming a pH-sensitive borate ester bond to give the functionalized PPNCs prodrugs. The potential of the PPNCs prodrugs on tumor cells therapy was systematically evaluated in dose/time-dependent effects. In vitro results showed a rapid accumulation of the prodrugs into the MDA-MB-231 tumor cell during the first 30 min and reached maximum at 24 h. Moreover, the cell-killing effect was observed quickly after 4 h incubation with an IC50 of 0.5 mg/mL (≈4 μM/L). In general, given the efficient pH-dependent DOX release of these constructed nanoconjugates, it is anticipated to contribute a potential delivery strategy for cancer therapy.
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Submitted on : Monday, October 25, 2021 - 2:15:05 PM
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Pei Zhou, Shuang Wu, Mohammad Hegazy, Hong Li, Xueju Xu, et al.. Engineered borate ester conjugated protein-polymer nanoconjugates for pH-responsive drug delivery. Materials Science and Engineering: C, Elsevier, 2019, 104, pp.109914. ⟨10.1016/j.msec.2019.109914⟩. ⟨hal-02378765⟩



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