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High-drug-loading capacity of redox-activated biodegradable nanoplatform for active targeted delivery of chemotherapeutic drugs.


ABSTRACT: Challenges associated with low-drug-loading capacity, lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy. Herein, we constructed active-targeting, redox-activated polymeric micelles (HPGssML) self-assembled aptamer-decorated, amphiphilic biodegradable poly (benzyl malolactonate-co-?-caprolactone) copolymer with disulfide linkage and ?-conjugated moieties. HPGssML with a homogenous spherical shape and nanosized diameter (?150?nm) formed a low critical micellar concentration (10-3?mg/mL), suggesting good stability of polymeric micelles. The anticancer drug, doxorubicin (DOX), can be efficiently loaded into the core of micelles with high-drug-loading content via strong ?-? interaction, which was verified by a decrease in fluorescence intensity and redshift in UV adsorption of DOX in micelles. The redox sensitivity of polymeric micelles was confirmed by size change and in vitro drug release in a reducing environment. Confocal microscopy and flow cytometry assay demonstrated that conjugating aptamers could enhance specific uptake of HPGssML by cancer cells. An in vitro cytotoxicity study showed that the half-maximal inhibitory concentration (IC50) of DOX-loaded HPGssML was two times lower than that of the control group, demonstrating improved antitumor efficacy. Therefore, the multifunctional biodegradable polymeric micelles can be exploited as a desirable drug carrier for effective cancer treatment.

SUBMITTER: Zhang H 

PROVIDER: S-EPMC7414993 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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High-drug-loading capacity of redox-activated biodegradable nanoplatform for active targeted delivery of chemotherapeutic drugs.

Zhang Hai H   Yan Jianqin J   Mei Heng H   Cai Shengsheng S   Li Sai S   Cheng Furong F   Cao Jun J   He Bin B  

Regenerative biomaterials 20200706 4


Challenges associated with low-drug-loading capacity, lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy. Herein, we constructed active-targeting, redox-activated polymeric micelles (HPGssML) self-assembled aptamer-decorated, amphiphilic biodegradable poly (benzyl malolactonate-co-ε-caprolactone) copolymer with disulfide linkage and π-conjugated moieties. HPGssML with a homogenous spherical shape and nanosized di  ...[more]

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