Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Coloading Rapa and Res into liposomes to promote apoptosis and ferroptosis in tumor cells represents a promising strategy for the treatment of colorectal cancer.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Coloading Rapa and Res into liposomes to promote apoptosis and ferroptosis in tumor cells represents a promising strategy for the treatment of colorectal cancer.
摘要：
目的：单药治疗结直肠癌通常无效。在这项研究中,我们开发了负载雷帕霉素（Rapa）和白藜芦醇（Res）的PEG修饰的脂质体（Rapa/Res脂质体，或RRL）来研究它们在结直肠癌中的治疗潜力。
方法：使用反相蒸发方法构建RRL。我们评估了细胞毒性，凋亡，和RRL对HCT116结直肠癌细胞的铁蛋白作用。在HCT116异种移植小鼠中评价RRL的抗肿瘤功效。
结果：RRL的粒径为86.67±1.10nm，ζ电位为-33.13±0.49mV。Coloaded制剂在体外和体内均表现出令人满意的性能，导致对HCT116结直肠癌细胞的细胞毒性增加，并显著抑制HCT116异种移植物肿瘤生长。机械上,RRL显著增加HCT116细胞的凋亡率，诱导ROS在肿瘤细胞中积累，并有效地下调了铁凋亡相关蛋白GPX4和SLC7A11的表达，证明了其与单独的Rapa脂质体（Rapa/Lps）或Res脂质体（Res/Lps）相比的优异功效。
结论：将Rapa和Res吸入脂质体以促进肿瘤细胞的凋亡和铁凋亡是治疗结直肠癌的一种有希望的策略。
方法：使用反相蒸发方法构建RRL。我们评估了细胞毒性，凋亡，和RRL对HCT116结直肠癌细胞的铁蛋白作用。在HCT116异种移植小鼠中评价RRL的抗肿瘤功效。
结果：RRL的粒径为86.67±1.10nm，ζ电位为-33.13±0.49mV。Coloaded制剂在体外和体内均表现出令人满意的性能，导致对HCT116结直肠癌细胞的细胞毒性增加，并显著抑制HCT116异种移植物肿瘤生长。机械上,RRL显著增加HCT116细胞的凋亡率，诱导ROS在肿瘤细胞中积累，并有效地下调了铁凋亡相关蛋白GPX4和SLC7A11的表达，证明了其与单独的Rapa脂质体（Rapa/Lps）或Res脂质体（Res/Lps）相比的优异功效。
结论：将Rapa和Res吸入脂质体以促进肿瘤细胞的凋亡和铁凋亡是治疗结直肠癌的一种有希望的策略。
