鉴于癌相关成纤维细胞（CAFs）在塑造肿瘤基质中的关键作用，本研究展示了一种CAF相关的ITGB1失活肽富集的纳米递送系统（命名为PMNPs-D），以同时靶向CAF和肿瘤细胞，通过促进药物灌注来增强化疗效果。在PMNPs-D的结构中，基于PLGA的内核负载了化疗药物多柔比星，外表面被插入整合素β1（ITGB1）抑制肽（即FNIII14）的混合生物膜所包裹。经过长时间的血液循环和积极靶向肿瘤部位后，PMNPs-D能够响应CAF过表达的成纤维细胞活化蛋白-α（FAP-α），触发FNIII14的释放，该肽将与ITGB1结合并抑制CAF在产生基质上的生物学功能，从而松弛致密的基质结构，增强纳米治疗药物在肿瘤中的渗透性。结果在携带恶性腺样囊性癌（ACC）的肿瘤模型小鼠中，这种定制设计的纳米系统显示了显著的肿瘤抑制和转移延缓效果。

Given the key roles of cancer associated fibroblasts (CAFs) in shaping tumor stroma, this study shows a CAF-associated ITGB1-inactivating peptide-enriched membrane nanodelivery system (designated as PMNPs-D) to simultaneously target CAFs and tumor cells for boosted chemotherapy through promoted drug perfusion. In the structure of PMNPs-D, the PLGA-based inner core is loaded with the chemotherapeutic drug doxorubicin, and the outer surface is cloaked by hybrid biomembranes with the insertion of integrin β1 (ITGB1) inhibiting peptide (i.e., FNIII14). After prolonged blood circulation and actively targeting in tumor sites, PMNPs-D can respond to CAF-overexpressed fibroblast activation protein-α (FAP-α) to trigger the release of FNIII14, which will bind to ITGB1 and inhibit CAFs' biological function in producing the stromal matrix, thereby loosening the condensed stromal structure and enhancing the permeability of nanotherapeutics in tumors. As a result, this tailor-designed nanosystem shows substantial tumor inhibition and metastasis retardation in aggressive adenoid cystic carcinoma (ACC) tumor-harboring mice.