Reduction-responsive polypeptide nanomedicines significantly inhibit progression of orthotopic osteosarcoma
Reduction-responsive polypeptide nanomedicines significantly inhibit progression of orthotopic osteosarcoma
复制标题
还原反应性多肽纳米药物显着抑制原位骨肉瘤的进展
DOI：
10.1016/j.nano.2019.102085
复制
发表时间：
2020-01-01
影响因子：
5.4
通讯作者：
Ding, Jianxun
中科院分区：
文献类型：
--
作者：
Yin, Fei;Wang, Zongyi;Ding, Jianxun
骨肉瘤(OS)是最常见的恶性骨肿瘤，具有较高的转移率和死亡率。新辅助化疗是一种有效的治疗方案，但疗效不佳，副作用较大，限制了其临床应用。本研究开发了基于甲氧基多柔比星(glycol)-block-poly(S-tert-butylmercapto-L-cysteine))的还原响应型多肽胶束，以控制阿霉素在OS治疗中的释放。与游离DOX相比，P4M/DOX和P9M/DOX的药代动力学曲线下面积分别增加2.6和3.5倍，肿瘤积聚增加1.6和2.0倍，心脏分布减少1.6和1.7倍。此外，胶束在肿瘤中的选择性聚集，特别是P9M/DOX，对原发和肺转移的OSS均有较强的抗肿瘤作用，且全身毒性较小。这些胶束对细胞内微环境具有灵敏的响应性，在癌症治疗的临床化疗药物靶向输送方面具有很高的前景。(C)2019 Elsevier Inc.保留所有权利。
Osteosarcoma (OS) is the most common malignant bone tumor with high metastasis and mortality. Neoadjuvant chemotherapy is an effective therapeutic regimen, but the clinical application is limited by the unsatisfactory efficacies and considerable side effects. In this study, the reduction-responsive polypeptide micelles based on methoxy poly(ethylene glycol)-block-poly(S-tert-butylmercapto-L-cysteine) copolymers (mPEG(113)-b-PBMLC4, P4M, and mPEG(113)-b-PBMLC9, P9M) were developed to control the delivery of doxorubicin (DOX) in OS therapy. Compared to free DOX, P4M/DOX and P9M/DOX exhibited 2.6 and 3.5 times increase in the area under the curve of pharmacokinetics, 1.6 and 2.0 times increase in tumor accumulation, and 1.6 and 1.7 times decrease of the distribution in the heart. Moreover, the selective accumulation of micelles, especially P9M/DOX, in tumors induced stronger antitumor effects on both primary and lung metastatic OSs with less systematic toxicity. These micelles with smart responsiveness to intracellular microenvironments are highly promising for the targeted delivery of clinical chemotherapeutic drugs in cancer therapy. (c) 2019 Elsevier Inc. All rights reserved.