Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, College of Chemistry & Environmental Science, Chemical Biology Key Laboratory of Hebei Province, Institute of Life Science and Green Development, Hebei University, Baoding, 071002, PR China.
College of Basic Medical Science, Key Laboratory of Pathogenesis Mechanism and Control of Inflammatory-autoimmune Diseases of Hebei Province, Hebei University, Baoding, 071002, PR China.
Biomaterials. 2021 Aug;275:120992. doi: 10.1016/j.biomaterials.2021.120992. Epub 2021 Jun 24.
Postoperative recurrence at the primary site and distant metastasis remains the challenge in treating triple-negative breast cancer due to its unpredictable invasion into adjacent tissues. Although systemic chemotherapy has been extensively adopted to attenuate the recurrence and metastasis, the abundant nutrition supply by blood vessels would promote the rapid proliferation of tumor cells and angiogenesis. Herein, we reported a nutrition deprivation strategy by ambidextrously blocking the residual blood vessels and inhibiting angiogenesis to realize efficient treatment of triple-negative breast cancer. To this end, an injectable hydrogel with photo-responsive property was prepared by using polydopamine crosslinked collagen/silk fibroin composite to deliver thrombin for blocking blood vessels and angiogenesis. In the presence of NIR light, the locked thrombin was released into the blood vessels in the adjacent tissues to promote blood coagulation. In addition, the photothermal effect would reduce the secreting of VEGF for preventing angiogenesis in the adjacent tissues. The in vitro and in vivo results demonstrated that the permanent interruption of nutrient supply by blocking the blood vessels adjacent to the resected tumor and preventing angiogenesis is a promising strategy to prevent the recurrence and metastasis of TNBC.
由于三阴性乳腺癌(TNBC)具有不可预测的侵袭性,使其在原发部位的术后复发和远处转移仍然是治疗的挑战。尽管系统化疗已广泛用于减轻复发和转移,但血管提供的丰富营养供应会促进肿瘤细胞的快速增殖和血管生成。在这里,我们报告了一种通过双管齐下地阻断残留血管和抑制血管生成来实现有效治疗三阴性乳腺癌的营养剥夺策略。为此,我们通过使用聚多巴胺交联的胶原/丝素复合水凝胶制备了一种具有光响应性的可注射水凝胶,以递送凝血酶来阻断血管和血管生成。在近红外光(NIR)的存在下,锁定的凝血酶被释放到相邻组织中的血管中,以促进血液凝固。此外,光热效应会减少 VEGF 的分泌,从而防止相邻组织中的血管生成。体外和体内结果表明,通过阻断切除肿瘤相邻的血管并防止血管生成来永久中断营养供应是预防 TNBC 复发和转移的一种有前途的策略。