Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Tongren Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200050, China.
Mol Pharm. 2022 Aug 1;19(8):2840-2853. doi: 10.1021/acs.molpharmaceut.2c00212. Epub 2022 Jul 18.
Some cancer cell membrane (CCM)-derived nanovesicles show strong homing effects and are used for targeted cancer therapy. By co-constructing the B16F10 cell membrane with a PEGylated phospholipid membrane, a new nanocarrier with a composite nanocrown structure was developed, which can evade immune recognition and actively target homologous melanoma. The nanocrowns have an encapsulation efficiency of more than 90% for paclitaxel and showed no significant difference ( > 0.05) from the PEGylated phospholipid membrane vesicles. Compared with the hyaluronic acid-modified PEGylated phospholipid membrane vesicles, the biomimetic nanocrowns enhanced the escape of nanovesicles from reticuloendothelial cells in vitro and extended the circulation time in vivo; moreover, the nanocrowns showed superior melanoma-targeted drug delivery capability and improved anticancer effects of paclitaxel as demonstrated by the inhibition of B16F10 cell proliferation and induction of apoptosis by interfering with microtubule formation. In contrast, the modification of hyaluronic acid did not increase the targeting capacity or antitumor effects of the nanocrowns, confirming that the superior targeting capacity was mediated by the exposed homologous CCMs rather than by hyaluronic acid. Our results demonstrate the potential of using biomimetic nanocrowns for active melanoma-targeted therapy.
一些癌细胞膜(CCM)衍生的纳米囊泡显示出强烈的归巢效应,可用于靶向癌症治疗。通过将 B16F10 细胞膜与聚乙二醇化磷脂膜共同构建,开发了一种具有复合纳米冠结构的新型纳米载体,该载体可以逃避免疫识别并主动靶向同源性黑色素瘤。纳米冠对紫杉醇的包封效率超过 90%,与聚乙二醇化磷脂膜囊泡相比没有显著差异(> 0.05)。与透明质酸修饰的聚乙二醇化磷脂膜囊相比,仿生纳米冠增强了纳米囊从网状内皮细胞中的逃逸,并延长了体内循环时间;此外,纳米冠表现出优越的黑色素瘤靶向药物传递能力,并通过干扰微管形成来提高紫杉醇的抗癌效果,从而抑制了 B16F10 细胞的增殖并诱导了细胞凋亡。相比之下,透明质酸的修饰并没有增加纳米冠的靶向能力或抗肿瘤效果,这证实了优越的靶向能力是由暴露的同源 CCM 介导的,而不是由透明质酸介导的。我们的结果表明,使用仿生纳米冠进行主动黑色素瘤靶向治疗具有潜力。