Huang Na, Liu Yuqing, Fang Yisheng, Zheng Siting, Wu Jianhua, Wang Miaohong, Zhong Wen, Shi Min, Xing Malcolm, Liao Wangjun
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People's Republic of China.
Department of Mechanical Engineering, Faculty of Agriculture, University of Manitoba, Winnipeg R3T2N2, Canada.
ACS Nano. 2020 Jul 28;14(7):7940-7958. doi: 10.1021/acsnano.9b08460. Epub 2020 Jun 15.
Gold nanoparticles (AuNPs) are a promising nanomaterial due to their drug-delivery properties and inherent anti-neoplastic activity. Here, we focused on the anti-neoplastic effects of an improved targeting polymer and folic acid-modified gold nanoparticles (AuNPP-FA) without therapeutic drugs. AuNPP-FA inhibited tumor proliferation both and , and tumor metastasis was controlled . We also found that, in addition to inhibiting tumor angiogenesis, AuNPP-FA normalized tumor vasculature by increasing pericyte coverage and strengthening tight junctions by upregulating VE-cadherin (VE-cad) levels on endothelial cells. This decreased vascular permeability, improved vascular perfusion, and alleviated tissue hypoxia. The immunotherapeutic response was enhanced due to the increased infiltration of CD3CD8 T lymphocytes. AuNPP-FA increased the expression and secretion of semaphorin 3A (SEMA3A) in cancer cells to further inhibit Smad2/3 signaling in human umbilical vein endothelial cells (HUVECs). This normalized tumor vasculature and inhibited metastasis. In conclusion, AuNPP-FA normalized tumor vasculature; therefore, AuNPP-FA has great potential for future clinical applications.
金纳米颗粒（AuNPs）因其药物递送特性和固有的抗肿瘤活性而成为一种有前景的纳米材料。在此，我们聚焦于一种改良的靶向聚合物和叶酸修饰的金纳米颗粒（AuNPP-FA）在无治疗药物情况下的抗肿瘤作用。AuNPP-FA在体内和体外均抑制肿瘤增殖，并控制肿瘤转移。我们还发现，除了抑制肿瘤血管生成外，AuNPP-FA通过增加周细胞覆盖和上调内皮细胞上的血管内皮钙黏蛋白（VE-cad）水平来加强紧密连接，从而使肿瘤血管正常化。这降低了血管通透性，改善了血管灌注，并减轻了组织缺氧。由于CD3CD8 T淋巴细胞浸润增加，免疫治疗反应得到增强。AuNPP-FA增加癌细胞中信号素3A（SEMA3A）的表达和分泌，以进一步抑制人脐静脉内皮细胞（HUVECs）中的Smad2/3信号传导。这使肿瘤血管正常化并抑制转移。总之，AuNPP-FA使肿瘤血管正常化；因此，AuNPP-FA在未来临床应用中具有巨大潜力。
