Deformable liposomal codelivery of vorinostat and simvastatin promotes antitumor responses through remodeling tumor microenvironment,Biomaterials Science

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Deformable liposomal codelivery of vorinostat and simvastatin promotes antitumor responses through remodeling tumor microenvironment
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-11-10 , DOI: 10.1039/d0bm01516d
Bin Tu _{1,

2,

3,

4,

5} , Yang He _{1,

2,

3,

4,

5} , Binfan Chen _{1,

2,

3,

4,

5} , Yonghui Wang _{1,

2,

3,

4,

5} , Yanrong Gao _{1,

2,

3,

4,

5} , Mingjie Shi _{1,

2,

3,

4,

5} , Tuanbing Liu _{1,

2,

3,

4,

5} , Akmal M. Asrorov _{1,

2,

3,

4,

5} , Yongzhuo Huang _{1,

2,

3,

4,

5}

Affiliation

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.

中文翻译：

伏立诺他和辛伐他汀的可变形脂质体代码传递通过重塑肿瘤微环境促进抗肿瘤反应

肿瘤微环境（TME）及其主要成分与肿瘤相关的巨噬细胞（TAM）在非小细胞肺癌（NSCLC）的发展中起着关键作用。提出了基于表观遗传学的基于药物的联合治疗策略，并开发了可变形脂质体系统（D-Lipo）用于伏立诺他和辛伐他汀代码传递以重塑TME。可变形脂质体在全身性癌症药物输送中的应用尚未得到充分的研究，其在癌症治疗中的潜力尚不清楚。这项工作表明D-Lipo表现出增强的肿瘤内浸润能力。拟议的治疗策略的特点是无化学疗法和TME重塑功能。D-Lipo有效抑制异种移植肺肿瘤的生长。抗肿瘤机制涉及TAM从M2型重新极化为M1型，抗血管生成以及随后的TME重塑。结果，抗肿瘤M1巨噬细胞和细胞毒性CD8的量⁺ T细胞增加，而促肿瘤M2巨噬细胞和调节性T细胞（Tregs）的数量减少。它为治疗实体瘤的基于表观遗传学的药物联合治疗提供了有希望的途径。

更新日期：2020-11-12

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