原位纳米平台协同中性粒细胞干预和化疗预防术后肿瘤复发和转移。

In-situ nanoplatform with synergistic neutrophil intervention and chemotherapy to prevent postoperative tumor recurrence and metastasis.

机构信息

National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.

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; Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medica, Huazhong University of Science and Technology, Wuhan 430074, China.

出版信息

J Control Release. 2024 Nov;375:316-330. doi: 10.1016/j.jconrel.2024.09.011. Epub 2024 Sep 17.

Abstract

In addition to residual tumor cells, surgery-induced inflammation significantly contributes to tumor recurrence and metastasis by recruiting polymorphonuclear neutrophils (PMNs) and promoting their involvement in tumor cell proliferation, invasion and immune evasion. Efficiently eliminating residual tumor cells while concurrently intervening in PMN function represents a promising approach for enhanced postoperative cancer treatment. Here, a chitosan/polyethylene oxide electrospun fibrous scaffold co-delivering celecoxib (CEL) and doxorubicin-loaded tumor cell-derived microparticles (DOX-MPs) is developed for postoperative in-situ treatment in breast cancer. This implant (CEL/DOX-MPs@CP) ensures prolonged drug retention and sustained release within the surgical tumor cavity. The released DOX-MPs effectively eliminate residual tumor cells, while the released CEL inhibits the function of inflammatory PMNs, suppressing their promotion of residual tumor cell proliferation, migration and invasion, as well as remodeling the tumor immune microenvironment. Importantly, the strategy is closely associated with interference in neutrophil extracellular trap (NET) released from inflammatory PMNs, leading to a substantial reduction in postoperative tumor recurrence and metastasis. Our results demonstrate that CEL/DOX-MPs@CP holds great promise as an implant to enhance the prognosis of breast cancer patients following surgery.

摘要

除了残留的肿瘤细胞,手术引起的炎症通过招募多形核粒细胞(PMN)并促进其参与肿瘤细胞增殖、侵袭和免疫逃避,显著促进肿瘤复发和转移。在有效消除残留肿瘤细胞的同时干预 PMN 功能,是提高术后癌症治疗效果的一种有前途的方法。在这里,开发了一种壳聚糖/聚氧化乙烯电纺纤维支架,共同递送塞来昔布(CEL)和载多柔比星的肿瘤细胞衍生微粒(DOX-MPs),用于乳腺癌术后原位治疗。这种植入物(CEL/DOX-MPs@CP)确保了药物在手术肿瘤腔内的长时间保留和持续释放。释放的 DOX-MPs 能有效消除残留的肿瘤细胞,而释放的 CEL 抑制炎性 PMN 的功能,抑制其对残留肿瘤细胞增殖、迁移和侵袭的促进作用,并重塑肿瘤免疫微环境。重要的是,该策略与干扰炎性 PMN 释放的中性粒细胞胞外陷阱(NET)密切相关,从而显著降低术后肿瘤复发和转移的风险。我们的研究结果表明,CEL/DOX-MPs@CP 作为一种植入物具有很大的应用潜力,可以提高乳腺癌患者术后的预后。

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