College of Biology, Hunan University, Changsha, 410082, China.
Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
J Mater Chem B. 2021 May 12;9(18):3838-3855. doi: 10.1039/d1tb00029b.
Although drug combination has proved to be an efficient strategy for clinic gastric cancer therapy, how to further improve their bioavailability and reduce the side effects are still challenges due to the low solubility and untargeted ability of drugs. Recently, newly emerging nanotechnology has provided an alternative for constructing new drug delivery systems with high targeting ability and solubility. In this study, a pH-responsive liposome (Liposome-PEO, LP) loaded with apatinib (AP) and cinobufagin (CS-1) was used for combinational therapy against gastric cancer after coating with a hybrid membrane (R/C). The results indicated that the constructed nanocomplex LP-R/C@AC not only efficiently killed tumor cells in vitro by inducing apoptosis, autophagy, and pyroptosis, but also significantly inhibited tumor invasion and metastasis via the VEGFR2/STAT3 pathway. Moreover, it showed stronger anti-tumor activity in gastric cancer-bearing mouse models, as compared to the sole drugs. A naturally-derived hybrid cell membrane coating bestowed nanocomplexes with enhanced biointerfacing including prolonged circulation time and targeting ability.
尽管药物联合已被证明是治疗临床胃癌的有效策略，但由于药物的低溶解度和非靶向性，如何进一步提高其生物利用度和降低副作用仍然是挑战。最近，新兴的纳米技术为构建具有高靶向性和溶解度的新型药物输送系统提供了一种替代方法。在这项研究中，载有阿帕替尼（AP）和华蟾素（CS-1）的 pH 响应脂质体（Liposome-PEO，LP）通过混合膜（R/C）包被用于联合治疗胃癌。结果表明，构建的纳米复合物 LP-R/C@AC 不仅通过诱导细胞凋亡、自噬和细胞焦亡有效地杀死了体外肿瘤细胞，还通过 VEGFR2/STAT3 通路显著抑制了肿瘤的侵袭和转移。此外，与单独使用药物相比，它在荷瘤小鼠模型中表现出更强的抗肿瘤活性。天然衍生的混合细胞膜涂层赋予纳米复合物增强的生物界面相互作用，包括延长的循环时间和靶向能力。
