可植入三明治样支架/纤维复合材料时空递呈康普瑞汀 A4 和阿霉素用于有效抑制术后肿瘤复发。

Implantable Sandwich-like Scaffold/Fiber Composite Spatiotemporally Releasing Combretastatin A4 and Doxorubicin for Efficient Inhibition of Postoperative Tumor Recurrence.

机构信息

Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

Institute for Tissue Engineering and Regenerative Medicine, School of Biomedical Science, The Chinese University of Hong Kong, Hong Kong 999077, China.

出版信息

ACS Appl Mater Interfaces. 2022 Jun 22;14(24):27525-27537. doi: 10.1021/acsami.2c02103. Epub 2022 Jun 10.

Abstract

Tumor recurrence is a critical conundrum in the postoperative therapy, on account of severe bleeding with disseminated tumor cells, residual tumor cells, and the rich nutrient and oxygen supply transported to tumors by the abundant blood vessels. Biodegradable drug-loaded implants, inserted in the resection cavity right away upon the surgery, possess bleeding prevention and efficient chemotherapeutic capabilities, considered to be a promising strategy to efficiently inhibit the recurrence of the solid tumor. Here, we developed a sandwich-like composite consisting of the combretastatin A4 (CA4)-loaded 3D-printed scaffold and doxorubicin (DOX)-loaded electrospun fiber (Scaffold-CA4@Fiber-DOX), presenting hemostatic, chemotherapeutic, and antibacterial potencies. The lyophilized 3D-printed scaffold with a porous structure rapidly absorbed and clotted the blood cells and disseminated tumor cells to prevent bleeding and tumor metastasis. Subsequently, the preferentially released CA4 from the scaffold disrupted the microtubules of the vascular endothelial cell, resulting in vascular deformation and consequent insufficient nutrient supply to the solid tumor. The sustained release of DOX from the sandwiched electrospun fiber dramatically inhibited the peripheral tumor cell proliferation. This all-in-one multifunctional implant system, combining efficient vascular disruption and chemotherapy, provides a promising strategy for postoperative tumor therapy.

摘要

肿瘤复发是术后治疗的一个关键难题,这是由于严重出血、播散的肿瘤细胞、残留的肿瘤细胞以及丰富的血管向肿瘤输送的丰富的营养和氧气。可生物降解的载药植入物在手术后立即插入切除腔,具有止血和有效的化疗能力,被认为是有效抑制实体瘤复发的有前途的策略。在这里,我们开发了一种夹心复合材料,由负载 combretastatin A4(CA4)的 3D 打印支架和负载多柔比星(DOX)的电纺纤维(支架-CA4@纤维-DOX)组成,具有止血、化疗和抗菌作用。冻干的多孔结构 3D 打印支架可快速吸收和凝结血细胞和播散的肿瘤细胞,以防止出血和肿瘤转移。随后,支架中优先释放的 CA4 破坏了血管内皮细胞的微管,导致血管变形,进而导致实体瘤的营养供应不足。夹在中间的电纺纤维中持续释放的 DOX 可显著抑制周围肿瘤细胞的增殖。这种一体化多功能植入系统结合了高效的血管破坏和化疗,为术后肿瘤治疗提供了一种有前途的策略。

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