Leukocyte-mimicking Pluronic-lipid nanovesicle hybrids inhibit the growth and metastasis of breast cancer
Leukocyte-mimicking Pluronic-lipid nanovesicle hybrids inhibit the growth and metastasis of breast cancer
复制标题
模拟白细胞的普朗尼克-脂质纳米囊泡杂合体抑制乳腺癌的生长和转移
DOI：
10.1039/c8nr08936a
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发表时间：
2019-03-28
期刊：
影响因子：
6.7
通讯作者：
Sha, Xianyi
中科院分区：
文献类型：
--
作者：
Chen, Qinyue;Chen, Yiting;Sha, Xianyi
乳腺癌是严重威胁女性健康的疾病，肿瘤细胞的转移导致女性患者的高死亡率。有证据表明，白细胞通过粘附于炎性内皮细胞以及肿瘤细胞而被乳腺肿瘤募集。此外，已知Pluronic P123可有效减少基质金属蛋白酶（MMP），其在细胞外基质（ECM）的降解中起关键作用，从而帮助肿瘤细胞逃离原发部位。受这些机制的启发，我们通过将从白细胞中提取的膜蛋白与膜样囊泡整合，将Pluronic P123杂交在脂质双层中，建立了模拟白细胞的Pluronic-脂质纳米囊泡杂化物（LPL），而紫杉醇（PTX）被选择为模型药物。杂交囊泡与白细胞膜蛋白完美地结合，并且P123没有引起对脂质膜的破坏，白细胞的生物靶向能力和P123的MMP-9下调作用在LPL中完全保留。LPL在体外试验中表现出增强的细胞摄取和抗转移功效，同时通过生物分布试验也发现了显著的肿瘤靶向能力。体内实验结果显示，载PTX的LPL对肿瘤生长的抑制率为80.84%，肺转移率为10.62%。此外，PTX-LPL大大降低了肿瘤以及肺中MMP-9和中性粒细胞的量。总之，LPL可能在转移性乳腺癌治疗中具有潜在的应用价值。
Breast cancer is a severe threat to the health of women, and the metastasis of tumor cells leads to high mortality in female patients. Evidence shows that leukocytes are recruited by breast tumors through adhesion to inflammatory endothelial cells as well as tumor cells. Moreover, it is known that Pluronic P123 is effective in the reduction of matrix metalloproteinases (MMPs), which play a key role in the degradation of the extracellular matrix (ECM), therefore helping tumor cells to escape from the primary site. Inspired by these mechanisms, we established a leukocyte-mimicking Pluronic-lipid nanovesicle hybrid (LPL) through integrating the membrane proteins extracted from leukocytes with membrane-like vesicles, with Pluronic P123 hybridized in the lipid bilayer, while paclitaxel (PTX) was selected as the model drug. The hybrid vesicles were perfectly incorporated with the leukocyte membrane proteins, and no disruption to the lipid membrane was caused by P123, with the bio-targeting ability of leukocytes and the MMP-9-downregulation effect of P123 fully preserved in LPL. LPL exhibited enhanced cellular uptake and anti-metastasis efficacy in in vitro assays, while significant tumor targeting capabilities were also found through biodistribution assays. Moreover, the in vivo therapeutic effects of PTX-loaded LPL (PTX-LPL) were observed, with an 80.84% inhibition rate of tumor growth and a 10.62% metastatic rate of tumor foci in lung tissue. Furthermore, the amounts of MMP-9 and neutrophils in the tumor as well as in the lung were greatly reduced with PTX-LPL. In summary, LPL may have potential applications in metastatic breast cancer therapy.