传统结直肠癌（CRC）化疗虽然具有疗效，但由于其有限的靶向能力、选择性不足以及与化疗相关的副作用，而令人沮丧。随着纳米医学的出现，利用一种脂质体递送系统来使用综合抗癌植物化学物质的组合，正在快速成为结直肠癌治疗中最具前景的纳米平台之一。越来越多的证据支持像川贝母甙这样的植物化学物质，因其抗癌效力而备受认可。为此，一种包含靶向肿瘤脂质体和植物化学物质的联合治疗可能具有更大的治疗潜力。在本研究中，我们开发了酸度诱导的合理膜（ATRAM），以及结合的川贝二号皂苷D2（PCD2）和脂质体（PCD2-Lipo-ATRAM）作为靶向肿瘤疗法。PCD2-Lipo-ATRAM治疗在CRC异种移植瘤中展示了成功的靶向肿瘤能力，其中PCD2不仅通过诱导凋亡细胞死亡发挥了强效抗肿瘤作用，而且还起到了脂质体膜稳定剂的作用。此外，PCD2-Lipo-ATRAM抑制了抗凋亡BCL-2蛋白家族，通过诱导内在性Caspase-9/-3介导的凋亡进一步增强了对CRC细胞的细胞毒作用。因此，我们的数据显示，基于靶向肿瘤的PCD2脂质体系统代表了一种有前景的结直肠癌治疗策略，因为它们直接靶向肿瘤，而不像其他治疗方法可能会错过目标。© 2023 作者

Conventional chemotherapy for colorectal cancer (CRC), though efficacious, is discouraging due to its limited targeting capability, lack of selectivity, and chemotherapy-associated side effects. With the advent of nanomedicines, a liposomal delivery system making use of a combination of anticancer phytochemicals is fast gaining popularity as one of the most promising nanoplatforms for CRC treatment. Rising evidence supports phytochemicals such as platycosides for their anticancer potency. To this end, a combination therapy including tumor-targeted liposomes along with phytochemicals might have a greater therapeutic potential against cancer. In this study, we developed acidity-triggered rational membrane (ATRAM) along with conjugated platycodin D2 (PCD2) and liposomes (PCD2-Lipo-ATRAM) as a tumor-targeting therapy. The PCD2-Lipo-ATRAM treatment demonstrated a successful tumor-targeting ability in the CRC xenografts, in which PCD2 not only exerted a potent antitumor effect by inducing apoptotic cell death and but also functioned as a liposome membrane stabilizer. Moreover, PCD2-Lipo-ATRAM suppressed antiapoptotic BCL-2 family proteins, resulting in enhanced cytotoxicity toward CRC cells by inducing intrinsic caspase-9/-3 mediated apoptosis. Thus, our data has shown that tumor-targeting PCD2-based liposomal systems represent a promising strategy for CRC therapy, since they directly target the tumors, unlike other therapies that can miss the target.© 2023 The Author(s).