载姜黄素高密度脂蛋白的合成与表征及其对宫颈癌细胞和宫颈癌干细胞的作用。
Synthesis and Characterization of Salinomycin-Loaded High-Density Lipoprotein and Its Effects on Cervical Cancer Cells and Cervical Cancer Stem Cells.
机构信息
Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, People's Republic of China.
Department of Medical Science, Chang Chun Medical College, Changchun, People's Republic of China.
出版信息
Int J Nanomedicine. 2021 Sep 17;16:6367-6382. doi: 10.2147/IJN.S326089. eCollection 2021.
BACKGROUND
Cervical cancer stem cells (CCSCs), a small part of tumor population, are one of the important reasons for metastasis and recurrence of cervical cancer. Targeting CCSCs may be an effective way to eliminate tumors. Salinomycin (Sal) has been proved to be an effective anticancer drug in many studies, especially for cancer stem cells (CSCs). However, the cytotoxicity of salinomycin limits its further research as an anticancer drug. High-density lipoprotein (HDL) nanoparticles are an excellent drug carrier, which can reduce the toxicity of Sal, have a certain targeting effect and improve the clinical benefit of Sal.
METHODS
Salinomycin-loaded high-density lipoprotein (S-HDL) was synthesized and characterized by various analytical techniques. CD44CD24 CCSCs were isolated from HeLa cells by magnetic separation. The uptake of HDL nanoparticles was observed by laser confocal microscopy, and the effect of S-HDL on the proliferation of CCCs and CCSCs was detected by cell viability analysis. Genome-wide analysis was used to analyze the effects of S-HDL on the biological processes of CCCs and then cell apoptosis, cell cycle and cell migration were selected for verification.
RESULTS
S-HDL had a particle size of 38.98 ± 1.78 nm and an encapsulation efficiency of 50.73 ± 4.29%. Cell uptake analysis showed that HDL nanoparticles could enhance the drug uptake of CCCs and CCSCs and may target CCCs and CCSCs. In cell viability analysis, CCCs and CCSCs showed high sensitivity to S-HDL. S-HDL can more efficiently prevent CCSCs from developing tumorspheres than Sal in tumorsphere formation study. S-HDL had stronger ability to induce cell cycle arrest, promote cell apoptosis and inhibit cell migration compared with free Sal, which was consistent with the results of Genome Wide analysis.
CONCLUSION
S-HDL can effectively target and eliminate CCCs and CCSCs, which is a potential drug for the treatment of cervical cancer.
背景
宫颈癌干细胞（CCSCs）是肿瘤细胞群体中的一小部分，是宫颈癌转移和复发的重要原因之一。针对 CCSCs 可能是消除肿瘤的有效方法。在许多研究中，沙利霉素（Sal）已被证明是一种有效的抗癌药物，特别是对癌症干细胞（CSCs）。然而，沙利霉素的细胞毒性限制了其作为抗癌药物的进一步研究。高密度脂蛋白（HDL）纳米颗粒是一种极好的药物载体，它可以降低 Sal 的毒性，具有一定的靶向作用，并提高 Sal 的临床获益。
方法
采用多种分析技术合成并表征载沙利霉素的高密度脂蛋白（S-HDL）。通过磁分离从 HeLa 细胞中分离出 CD44CD24 CCSCs。激光共聚焦显微镜观察 HDL 纳米颗粒的摄取，细胞活力分析检测 S-HDL 对 CCCs 和 CCSCs 增殖的影响。全基因组分析用于分析 S-HDL 对 CCCs 生物学过程的影响，然后选择细胞凋亡、细胞周期和细胞迁移进行验证。
结果
S-HDL 的粒径为 38.98 ± 1.78nm，包封率为 50.73 ± 4.29%。细胞摄取分析表明，HDL 纳米颗粒可以增强 CCCs 和 CCSCs 的药物摄取，可能靶向 CCCs 和 CCSCs。在细胞活力分析中，CCCs 和 CCSCs 对 S-HDL 表现出高敏感性。与 Sal 相比，S-HDL 在肿瘤球体形成研究中更有效地阻止 CCSCs 形成肿瘤球体。S-HDL 诱导细胞周期停滞、促进细胞凋亡和抑制细胞迁移的能力均强于游离 Sal，与全基因组分析结果一致。
结论
S-HDL 能有效靶向和消除 CCCs 和 CCSCs，是治疗宫颈癌的潜在药物。
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