由于耐药性的发展，单靶点抑制剂在癌症治疗中尚未取得成功。然而，能够同时抑制多个靶标的治疗剂在诱导癌细胞凋亡和克服癌细胞耐药性方面显示出令人鼓舞的结果。在这里，我们设计了一种复合脂质体纳米载体，共同负载 5-氟尿嘧啶 (5-FU) 和全反式视黄酸 (ATRA)，以评估组合药物在结直肠癌 (CRC) 中的抗癌功效。通过薄膜水合技术合成了磷脂/胆固醇/DSPE-PEG (2000) 载体，用于 ATRA 和 5-FU 的共同递送。表征后，通过集落形成和 MTT 法研究了 5-FU 和 ATRA 共载脂质体纳米载体在增殖、上皮间质转化 (EMT)、凋亡和癌症干细胞 (CSC) 中的作用，RT- qPCR和Annexin V/PI试剂盒。脂质体(LPs)的平均粒径为 < 150 nm，粒径分布均匀。药物释放分析表明，ATRA 和 5-FU 可以同时从 LP 中以缓释方式释放。验证了LPs负载的ATRA和5-FU的协同抑制作用，组合指数为0.43。双药 LP 显示出最高的细胞毒性、增强的细胞增殖抑制、增加的凋亡潜力、减少的 CSC 以及减弱的 EMT 相关生物标志物。此外，双药 LP 比其他脂质体制剂更能降低 β-catenin 基因表达。这些研究结果表明，使用 LP 实现 ATRA 和 5-FU 的协同作用是提高 5-FU 对 CRC 细胞治疗效果的有效方法.© 2023。作者获得 Springer Nature B.V. 的独家许可。

Single-target inhibitors have not been successful in cancer treatment due to the development of drug resistance. Nevertheless, therapeutic agents capable of simultaneously inhibiting multiple targets have revealed encouraging results in inducing apoptosis and overcoming drug resistance in cancerous cells. Here, we designed a composite liposomal nano-carrier co-loading 5-Fluorouracil (5-FU) with all-trans retinoic acid (ATRA) to assess anticancer efficacy of the combined drugs in colorectal cancer (CRC).A PEGylated liposomal nano-carrier with phospholipid/cholesterol/DSPE-PEG (2000) was synthesized by the thin film hydration technique for co-delivery of ATRA and 5-FU. After characterizing, the role of 5-FU and ATRA co-loaded liposomal nano-carrier in proliferation, epithelial-mesenchymal transition (EMT), apoptosis, and cancer stem cells (CSCs) were investigated by using colony forming and MTT assay, RT-qPCR and Annexin V/PI kit.The average size of liposomes (LPs) was < 150 nm with uniform size distribution. Drug release analyses indicated that both ATRA and 5-FU could simultaneously release from LPs in a sustained release manner. The synergistic inhibitory effects of ATRA and 5-FU loaded in LPs were verified with a combination index of 0.43. Dual drug LPs showed the highest cytotoxicity, enhanced inhibition of cell proliferation, increased apoptotic potential, decreased CSCs, and attenuated EMT-associated biomarkers. Also, dual drug LPs decreased β-catenin gene expression more than other liposomal formulations.These findings suggest that using LPs to achieve a synergistic effect of ATRA and 5-FU is an effectual approach to increase the therapeutic effect of 5-FU toward CRC cells.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.