Department of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangzhou, 510150, China.
Department of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangzhou, 510150, China.
J Pharm Sci. 2024 Aug;113(8):2565-2574. doi: 10.1016/j.xphs.2024.05.015. Epub 2024 May 19.
Monotherapy is often ineffective for treating colorectal cancer. In this study, we developed PEG-modified liposomes loaded with rapamycin (Rapa) and resveratrol (Res) (Rapa/Res liposomes, or RRL) to investigate their therapeutic potential in colorectal cancer.
RRL were constructed using the reversed-phase evaporation method. We assessed the cytotoxicity, apoptosis, and ferroptotic effects of RRL on colorectal cancer HCT116 cells. The anti-tumor efficacy of RRL was evaluated in HCT116 xenograft mice.
RRL had a particle size of 86.67 ± 1.10 nm and a zeta potential of -33.13 ± 0.49 mV. The coloaded formulation demonstrated satisfactory performance both in vitro and in vivo, resulting in increased cytotoxicity to HCT116 cells and significant suppression of HCT116 xenografts tumor growth. Mechanically, RRL significantly increased the apoptosis rate of HCT116 cells, induced ROS accumulation in tumor cells, and effectively downregulated the expression of the ferroptosis-associated proteins GPX4 and SLC7A11, demonstrating its superior efficacy compared to that of Rapa liposomes (Rapa/Lps) or Res liposomes (Res/Lps) alone.
Coloading Rapa and Res into liposomes to promote apoptosis and ferroptosis in tumor cells represents a promising strategy for the treatment of colorectal cancer.
单药治疗结肠癌往往效果不佳。本研究构建了载雷帕霉素（Rapa）和白藜芦醇（Res）的聚乙二醇修饰的脂质体（Rapa/Res 脂质体，或 RRL），旨在探讨其在结肠癌治疗中的潜在价值。
采用逆向蒸发法构建 RRL。评估 RRL 对结肠癌 HCT116 细胞的细胞毒性、细胞凋亡和铁死亡作用。在 HCT116 异种移植瘤小鼠中评价 RRL 的抗肿瘤疗效。
RRL 的粒径为 86.67±1.10nm，Zeta 电位为-33.13±0.49mV。共载体制剂在体内外均表现出良好的性能，导致 HCT116 细胞的细胞毒性增加，并显著抑制 HCT116 异种移植瘤的生长。机制上，RRL 显著增加 HCT116 细胞的凋亡率，诱导肿瘤细胞内 ROS 积累，并有效下调铁死亡相关蛋白 GPX4 和 SLC7A11 的表达，与单独的 Rapa 脂质体（Rapa/Lps）或 Res 脂质体（Res/Lps）相比，其疗效更优。
将 Rapa 和 Res 共载入脂质体以促进肿瘤细胞凋亡和铁死亡是治疗结肠癌的一种有前途的策略。
