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系统转移靶向纳米治疗增强肿瘤手术切除和化疗。

Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy.

机构信息

Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.

Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.

出版信息

Nat Commun. 2021 May 27;12(1):3187. doi: 10.1038/s41467-021-23466-5.

DOI:10.1038/s41467-021-23466-5
PMID:34045459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8160269/
Abstract

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form "micro-thrombi" with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of "micro-thrombi", and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.

摘要

传统的临床治疗方法（如肿瘤切除术和化疗）的失败主要是由于无法有效控制肿瘤转移。转移包括三个步骤：（i）肿瘤细胞通过上皮-间充质转化（EMT）从原发性部位逸出到循环系统，（ii）循环肿瘤细胞（CTC）与血小板形成“微血栓”以逃避循环中的免疫监视，以及（iii）CTC 定植于转移前生态位。在这里，我们设计了一种全身性转移靶向纳米治疗剂（H@CaPP），由抗炎剂白皮素和抗血栓剂低分子量肝素组成，以阻碍肿瘤转移的多个步骤。研究发现，H@CaPP 可有效抑制 EMT、抑制“微血栓”的形成，并防止转移前生态位的形成。当与手术切除或化疗联合使用时，H@CaPP 可有效抑制肿瘤转移并延长荷瘤小鼠的总生存期。总之，我们提供了一种简单有效的全身性转移靶向纳米治疗剂，用于治疗肿瘤转移。

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