<br>用整合素靶向肽-药物缀合物丝抑制内皮细胞介导的 T 淋巴细胞凋亡，用于三阴性乳腺癌的化学免疫治疗,Advanced Materials

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用整合素靶向肽-药物缀合物丝抑制内皮细胞介导的 T 淋巴细胞凋亡，用于三阴性乳腺癌的化学免疫治疗
Advanced Materials ( IF 27.4 ) Pub Date : 2023-10-17 , DOI: 10.1002/adma.202306676
Ying Cai _{1,

2} , Binyu Zhu _{1,

2} , Xiaoting Shan _{1,

2} , Lingli Zhou ₃ , Xujie Sun _{1,

2} , Anqi Xia _{1,

2} , Binhao Wu _{1,

2} , Yang Yu ₄ , Helen He Zhu ₅ , Pengcheng Zhang ₆ , Yaping Li _{1,

2,

3,

7,

8}

Affiliation

State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
National Facility for Protein Science in Shanghai, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, 201210, China.
State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200127, China.
School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai, 201210, China.
Shandong Laboratory of Yantai Drug Discovery, Bohai rim Advanced Research Institute for Drug Discovery, Shandong, 264000, China.
Yantai Key Laboratory of Nanomedicine and Advanced Preparations, Yantai Institute of Pharmaceutical Science, Shandong, 264000, China.

肿瘤相关内皮细胞 (TEC) 通过 Fas 配体 (FasL) 介导的机制诱导浸润性 T 淋巴细胞凋亡，从而限制抗肿瘤免疫。在此，这项工作通过谷胱甘肽响应性接头将 7-乙基-10-羟基喜树碱 (SN38) 连接到 C 末端带有 RGDR 或 HKD 基序的亲水片段，创建了肽-药物缀合物 (PDC)。 PDC 在水溶液中自发组装成细丝。含有 1% SN38-RGDR (SN38-HKD/RGDR) 的 PDC 丝有效靶向整合素表达上调的三阴性乳腺癌 (TNBC) 细胞和 TEC，并诱导肿瘤细胞的免疫原性细胞死亡 (ICD) 和 FasL 下调TEC。 SN38-HKD/RGDR 增加 CD8 ⁺ T 细胞的浸润、活性和活力，从而抑制原发肿瘤和肺转移的生长。这项研究强调了癌细胞和 TEC 与整合素靶向 PDC 丝的协同调节是 TNBC 化学免疫治疗的一种有前景的策略。

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更新日期：2023-10-17

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