Zhang Kuo, Yang Pei-Pei, He Ping-Ping, Wen Shi-Fang, Zou Xiao-Ran, Fan Yu, Chen Zi-Ming, Cao Hui, Yang Zhou, Yue Kai, Zhang Xinxin, Zhang Hua, Wang Lei, Wang Hao
Department of Materials Physics and Chemistry, School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China.
CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.
ACS Nano. 2020 Jun 23;14(6):7170-7180. doi: 10.1021/acsnano.0c02110. Epub 2020 May 19.
Cancer therapeutic strategies based on angiogenesis attract great attention from fundamental and clinical research. Blocking oxygen and nutrition supply to tumor cells could inhibit the growth of tumors based on occlusion of blood vessels in the tumor. Herein, we report a dual-responsive peptide-based nanoparticle, mimicking the laminin fibrillogenesis specifically and highly efficiently in tumor vessels, resulting in the blockage of tumor vessels and the growth inhibition of tumors. The laminin mimic peptide (LMMP) is designed with a fibrillation sequence, a pH-responsive sequence, and a targeting sequence. The LMMP in nanoformulations is delivered to blood vessels in the tumors, where the microenvironment (pH and microthrombus) enable LMMP to process laminin fibrillogenesis, constructing fibrous networks. The laminin-like fibrous networks capture red blood cells , forming occlusion specifically in the tumor blood vessels to inhibit the growth of the tumor.
基于血管生成的癌症治疗策略引起了基础研究和临床研究的广泛关注。通过阻断肿瘤血管来切断肿瘤细胞的氧气和营养供应，可以抑制肿瘤生长。在此，我们报告了一种基于双响应肽的纳米颗粒，它能在肿瘤血管中特异性且高效地模拟层粘连蛋白纤维形成，导致肿瘤血管阻塞和肿瘤生长抑制。层粘连蛋白模拟肽（LMMP）设计有一个纤维化序列、一个pH响应序列和一个靶向序列。纳米制剂中的LMMP被递送至肿瘤血管，在那里微环境（pH值和微血栓）促使LMMP进行层粘连蛋白纤维形成，构建纤维网络。类似层粘连蛋白的纤维网络捕获红细胞，在肿瘤血管中特异性形成阻塞，从而抑制肿瘤生长。
