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Enzyme Degradable Hyperbranched Polyphosphoester Micellar Nanomedicines for NIR Imaging-Guided Chemo-Photothermal Therapy of Drug-Resistant Cancers
Biomacromolecules ( IF 6.2 ) Pub Date : 2018-03-07 00:00:00 , DOI: 10.1021/acs.biomac.7b01793
Mengqun Yao 1, 2 , Yinchu Ma , Hang Liu , Malik Ihsanullah Khan , Song Shen , Shuya Li , Yangyang Zhao , Yi Liu , Guoqing Zhang , Xiaoqiu Li 1 , Fei Zhong 1, 2 , Wei Jiang , Yucai Wang
Affiliation  

Multidrug resistance (MDR) is the major cause for chemotherapy failure, which constitutes a formidable challenge in the field of cancer therapy. The synergistic chemo-photothermal treatment has been reported to be a potential strategy to overcome MDR. In this work, rationally designed enzyme-degradable, hyperbranched polyphosphoester nanomedicines were developed for reversing MDR via the codelivery of doxorubicin and IR-780 (hPPEDOX&IR) as combined chemo-photothermal therapy. The amphiphilic hyperbranched polyphosphoesters with phosphate bond as the branching point were synthesized via a simple but robust one-step polycondensation reaction. The self-assembled hPPEDOX&IR exhibited good serum stability, sustained release, preferable tumor accumulation, and enhanced drug influx of doxorubicin in resistant MCF-7/ADR cells. Moreover, the degradation of hPPEDOX&IR was accelerated in the presence of alkaline phosphatase, which was overexpressed in various cancers, resulting in the fast release of encapsulated doxorubicin. The enzyme-degradable polymer generated synergistic chemo-photothermal cytotoxicity against MCF-7/ADR cells and, thus, the efficient ablation of DOX-resistant tumor without regrowth. This delivery system may open a new avenue for codelivery of chemo- and photothermal therapeutics for MDR tumor therapy.

中文翻译:

酶可降解的超支化多聚磷酸酯胶束纳米药物用于近红外成像引导的化学光热疗法治疗耐药性癌症

多药耐药性(MDR)是化疗失败的主要原因,这在癌症治疗领域构成了巨大的挑战。协同化学光热疗法已被报道是克服MDR的潜在策略。在这项工作中,开发了经过合理设计的酶可降解,超支化的多磷酸酯纳米药物,用于通过阿霉素和IR-780(hPPE DOX&IR)的代码传递逆转MDR,作为化学光热疗法的联合疗法。通过简单但稳定的一步缩聚反应合成了以磷酸酯键为支化点的两亲性超支化聚磷酸酯。自组装hPPE DOX&IR在抗性MCF-7 / ADR细胞中表现出良好的血清稳定性,持续释放,优选的肿瘤蓄积和阿霉素的药物流入增加。此外,在碱性磷酸酶的存在下,hPPE DOX&IR的降解被加速,碱性磷酸酶在各种癌症中均过表达,从而导致胶囊化阿霉素的快速释放。可酶降解的聚合物对MCF-7 / ADR细胞产生协同的化学光热细胞毒性,因此可有效消融DOX耐药性肿瘤而无再生长。该递送系统可以为用于MDR肿瘤治疗的化学和光热疗法的代码递送开辟新的途径。
更新日期:2018-03-07
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