pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer

被引：22

作者：

Hao, Dan-Li ^{[1
]}

Xie, Ran ^{[1
]}

De, Ge-Jing ^{[1
]}

Yi, Hong ^{[1
]}

Zang, Chen ^{[1
]}

Yang, Mi-Yi ^{[1
]}

Liu, Li ^{[1
]}

Ma, Hai ^{[1
]}

Cai, Wei-Yan ^{[1
]}

Zhao, Qing-He ^{[1
]}

Sui, Feng ^{[1
]}

Chen, Yan-Jun ^{[1
]}

机构：

[1] China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

来源：

INTERNATIONAL JOURNAL OF NANOMEDICINE | 2020年 / 15卷

关键词：

artesunate; micelles; pH responsive; polymer prodrug; poly(2-ethyl-2-oxazoline); poly(beta-amino ester); IN-VITRO; BREAST-CANCER; ANTITUMOR-ACTIVITY; CONTROLLED-RELEASE; CELLS; ARTEMISININ; INHIBITION; APOPTOSIS; MICELLES; RESISTANCE;

D O I：

10.2147/IJN.S242032

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Purpose: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(beta-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model. Methods: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core. Results: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37 degrees C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%+/- 1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor. Conclusion: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.

引用

页码：1771 / 1786

页数：16

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