School of Pharmacy, Wannan Medical College, Wuhu, 241002, People's Republic of China.
Institute of Synthesis and Application of Medical Materials, Wannan Medical College, Wuhu, 241002, People's Republic of China.
Int J Nanomedicine. 2024 Jan 23;19:727-742. doi: 10.2147/IJN.S446895. eCollection 2024.
A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue.
TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L.
TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study.
Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.
顺序释放共递药系统是提高抗癌疗效的有效策略。本文构建了载有汉防己甲素（TET）和雷公藤红素（CEL）的苦参碱油质体（CTM）的多组分脂质体（TET-CTM/L），表现出协同抗肝癌活性。TET-CTM/L 凭借增强的通透性和保留效应（EPR）可在肿瘤部位实现高效积累。TET 首先被释放以修复异常血管并减少成纤维细胞，随后 CTM 被释放以消灭肿瘤组织。
采用 TEM（透射电子显微镜）和 DLS（动态光散射）对 TET-CTM/L 进行表征。采用流式细胞术检测 HepG2 细胞的细胞摄取和细胞毒性。采用 HepG2 异种移植裸鼠模型评估 TET-CTM/L 的抗肿瘤功效和全身安全性。
TET-CTM/L 的 TEM 图像显示 CTM 的小粒径结构位于大尺寸脂质体内部，表明 CTM 可以通过薄膜分散法被包裹在脂质体中。在体外研究中，TET-CTM/L 诱导 HepG2 细胞大量凋亡，表明对 HepG2 细胞具有协同细胞毒性。在体内研究中，与单独使用 celastrol 或 TET 相比，TET-CTM/L 显示出降低的系统毒性。在生物分布研究中，TET-CTM/L 显示出优异的肿瘤靶向能力。
本研究为联合抗癌治疗提供了一种新策略，不仅在肝癌治疗方面具有良好的应用前景，而且可以应用于其他实体瘤的治疗。
