National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Theranostics. 2022 Apr 24;12(7):3503-3517. doi: 10.7150/thno.69795. eCollection 2022.
The perioperative trauma-related platelet recruitment and activation severely affect tumor recurrence and metastasis. Therefore, efficiently killing residual tumor cells and simultaneously inhibiting platelet activation to block platelet-cancer cell interaction might be a promising strategy to prevent postoperative tumor recurrence and metastasis. Biodegradable PLGA electrospun nanofibrous films co-delivering doxorubicin-loaded tumor repopulating cell-derived microparticles (DOX-MPs) and aspirin (ASA) were developed as the implant materials (DOX-MPs/ASA@NF) for postoperative in-situ treatment. The characterization, cytotoxicity against tumor cells, inhibition in platelet activation-triggered proliferation, migration and metastasis of tumor cells and anti-recurrence and anti-metastasis activity induced by DOX-MPs/ASA@NF were systematically evaluated. PLGA nanofibrous films facilitate the enhanced distribution of DOX-MPs as well as DOX-MPs and ASA release in a time-programmed manner within the tumor resection cavity. The released DOX-MPs efficiently kill the residual tumor cells, while ASA decreases platelet activation and inhibits platelet-promoted proliferation, migration and metastasis of tumor cells, resulting in the remarkable inhibition of postoperative tumor recurrence and metastasis. DOX-MPs/ASA@NF may be a promising candidate to prevent the recurrence and metastasis of resectable tumors.
围手术期与创伤相关的血小板募集和激活严重影响肿瘤的复发和转移。因此，有效地杀伤残余肿瘤细胞，同时抑制血小板的激活以阻断血小板-肿瘤细胞相互作用，可能是预防术后肿瘤复发和转移的一种有前途的策略。我们开发了一种可生物降解的 PLGA 电纺纳米纤维膜，用于递送达泊昔单抗负载的肿瘤再群体细胞衍生的微粒（DOX-MPs）和阿司匹林（ASA），作为术后原位治疗的植入材料（DOX-MPs/ASA@NF）。我们系统地评估了 DOX-MPs/ASA@NF 的特征、对肿瘤细胞的细胞毒性、抑制血小板激活触发的肿瘤细胞增殖、迁移和转移的能力，以及诱导的抗复发和抗转移活性。PLGA 纳米纤维膜促进了 DOX-MPs 的增强分布，以及 DOX-MPs 和 ASA 以时间程序方式在肿瘤切除腔内释放。释放的 DOX-MPs 有效地杀伤残余肿瘤细胞，而 ASA 则降低了血小板的激活，并抑制了血小板促进的肿瘤细胞增殖、迁移和转移，从而显著抑制了术后肿瘤的复发和转移。DOX-MPs/ASA@NF 可能是预防可切除肿瘤复发和转移的一种有前途的候选药物。
