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载顺铂和多西紫杉醇的液晶纳米粒用于乳腺癌的靶向治疗。

Liquid crystalline nanoparticles encapsulating cisplatin and docetaxel combination for targeted therapy of breast cancer.

机构信息

College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongsanbuk-do, 712-749, South Korea.

College of Korean Medicine, Daegu Haany University, Gyeongsan, 712-702, South Korea.

出版信息

Biomater Sci. 2016 Aug 16;4(9):1340-50. doi: 10.1039/c6bm00376a.

Abstract

Cancer remains a leading cause of death. A combination of anticancer agents can effectively kill cancer through multiple pathways; however, improvements to their delivery are needed. Hence, docetaxel and cisplatin-loaded liquid crystalline nanoparticles with folic acid were prepared for effective and targeted anticancer therapy. Notably, hydroxypropyl-β-cyclodextrin/cisplatin complexes in 0.9% NaCl solution were used for the prevention of possible aquation of cisplatin, which would otherwise lead to severe adverse effects. The optimized nanoparticles exhibited small particle size, high drug loading capacity (>90%), and controlled drug release profiles. In vitro cell cytotoxicity assays demonstrated that the optimized nanoparticles were taken up by folate receptor-expressing cells to a greater extent than non-folate expressing cells, which is attributable to folate-specific endocytosis of the optimized nanoparticles. Enhanced expression of apoptotic markers (Bax, p21, and cleaved caspase-3) along with enhanced anti-migration effects in MDA-MB-231 cells following treatment suggests that the optimized nanoparticles provide an effective treatment for metastatic breast cancer. These results were further supported by in vivo findings obtained for a MDA-MB-231 tumor xenograft model. Altogether, the optimized nanoparticles may potentially be developed as an effective treatment modality for folate-targeted metastatic breast cancer treatment.

摘要

癌症仍然是主要的死亡原因。通过多种途径联合使用抗癌药物可以有效地杀死癌细胞;然而,需要改进它们的传递方式。因此,制备了载有紫杉醇和顺铂的具有叶酸的液晶纳米粒用于有效的靶向抗癌治疗。值得注意的是,在 0.9%NaCl 溶液中使用羟丙基-β-环糊精/顺铂复合物来预防顺铂可能的水合作用,否则会导致严重的不良反应。优化的纳米粒表现出较小的粒径、高载药量(>90%)和控制的药物释放曲线。体外细胞细胞毒性试验表明,优化的纳米粒被叶酸受体表达细胞摄取的程度大于非叶酸表达细胞,这归因于优化的纳米粒的叶酸特异性内吞作用。在 MDA-MB-231 细胞中,经处理后凋亡标志物(Bax、p21 和 cleaved caspase-3)的表达增强以及抗迁移作用增强,表明优化的纳米粒为转移性乳腺癌提供了有效的治疗。这些结果得到了 MDA-MB-231 肿瘤异种移植模型的体内研究结果的进一步支持。总的来说,优化的纳米粒可能有潜力被开发为叶酸靶向转移性乳腺癌治疗的有效治疗方式。

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