Tu Bin, He Yang, Chen Binfan, Wang Yonghui, Gao Yanrong, Shi Mingjie, Liu Tuanbing, Asrorov Akmal M, Huang Yongzhuo
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai 201203, China.
Biomater Sci. 2020 Dec 15;8(24):7166-7176. doi: 10.1039/d0bm01516d.
The tumor microenvironment (TME) and its major component tumor-associated macrophages (TAM) play a pivotal role in the development of non-small cell lung cancer (NSCLC). An epigenetic drug-based combinatory therapeutic strategy was proposed and a deformable liposome system (D-Lipo) was developed for vorinostat and simvastatin codelivery for remodeling the TME. The application of deformable liposomes in systemic cancer drug delivery has been underexplored and its potential in cancer therapy is largely unknown. This work revealed that D-Lipo exhibited an enhanced intratumor infiltration ability. The proposed therapeutic strategy was characterized by a chemo-free regimen and TME remodeling function. D-Lipo efficiently inhibited the growth of the xenografted lung tumor. The anti-tumor mechanisms involved the repolarization of TAM from the M2 to M1 phenotype, anti-angiogenesis, and the consequent TME remodeling. As a result, the amounts of the anti-tumor M1 macrophages and the cytotoxic CD8+ T cells increased, while the amounts of the pro-tumor M2 macrophages and regulatory T cells (Tregs) reduced. It provides a promising avenue for epigenetic drug-based combination therapy for treating solid tumors.
肿瘤微环境（TME）及其主要成分肿瘤相关巨噬细胞（TAM）在非小细胞肺癌（NSCLC）的发展中起关键作用。提出了一种基于表观遗传药物的联合治疗策略，并开发了一种可变形脂质体系统（D-Lipo）用于伏立诺他和辛伐他汀的共递送，以重塑TME。可变形脂质体在全身癌症药物递送中的应用尚未得到充分探索，其在癌症治疗中的潜力在很大程度上尚不清楚。这项工作表明，D-Lipo表现出增强的肿瘤内浸润能力。所提出的治疗策略的特点是无化疗方案和TME重塑功能。D-Lipo有效地抑制了异种移植肺肿瘤的生长。抗肿瘤机制包括TAM从M2表型向M1表型的重新极化、抗血管生成以及随之而来的TME重塑。结果，抗肿瘤M1巨噬细胞和细胞毒性CD8 + T细胞的数量增加，而促肿瘤M2巨噬细胞和调节性T细胞（Tregs）的数量减少。它为基于表观遗传药物的联合治疗实体瘤提供了一条有前景的途径。
