Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100, Granada, Spain.
Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071, Granada, Spain.
Sci Rep. 2017 Oct 18;7(1):13506. doi: 10.1038/s41598-017-13816-z.
Paclitaxel (PTX) is one of the drugs of choice in the treatment of breast and lung cancer. However, its severe side effects, including mielosuppression, cardiotoxicity and neurotoxicity, frequently cause treatment to be discontinued. Solid lipid nanoparticles (NPs) of glyceril tripalmitate (tripalmitin) loaded with PTX (Tripalm-NPs-PTX) including modifications by the addition of hexa(ethylene glycol), β-cyclodextrin and macelignan were developed. All NPs-PTX formulations displayed excellent hemocompatibility and significantly enhanced PTX antitumor activity in human breast (MCF7, MDAMB231, SKBR3 and T47D) and lung (A549, NCI-H520 and NCI-H460) cancer cells. Tripalm-NPs-PTX decreased PTX IC by as much as 40.5-fold in breast and 38.8-fold in lung cancer cells and Tripalm-NPs-PTX macelignan inhibited P-glycoprotein in resistant tumor cells. In addition, Tripalm-NPs-PTX significantly decreased the volume of breast and lung multicellular tumor spheroids that mimics in vivo tumor mass. Finally, Tripalm-NPs-PTX decreased the PTX IC of cancer stem cells (CSCs) derived from both lung and breast cancer cells (6.7- and 14.9-fold for MCF7 and A549 CSCs, respectively). These results offer a new PTX nanoformulation based on the use of tripalmitin which improves the antitumor activity of PTX and that may serve as an alternative PTX delivery system in breast and lung cancer treatment.
紫杉醇（PTX）是治疗乳腺癌和肺癌的首选药物之一。然而，其严重的副作用，包括骨髓抑制、心脏毒性和神经毒性，经常导致治疗中断。载紫杉醇的甘油三棕榈酸酯（三棕榈酸甘油酯）固体脂质纳米颗粒（NPs）（Tripalm-NPs-PTX）包括通过添加六乙二醇、β-环糊精和马钱子素进行修饰。所有 NPs-PTX 制剂均表现出良好的血液相容性，并显著增强了人乳腺癌（MCF7、MDAMB231、SKBR3 和 T47D）和肺癌（A549、NCI-H520 和 NCI-H460）癌细胞中 PTX 的抗肿瘤活性。Tripalm-NPs-PTX 在乳腺癌和肺癌细胞中使 PTX 的 IC 降低了多达 40.5 倍和 38.8 倍，并且 Tripalm-NPs-PTX 马钱子素抑制了耐药肿瘤细胞中的 P-糖蛋白。此外，Tripalm-NPs-PTX 显著减小了模拟体内肿瘤质量的乳腺癌和肺癌多细胞肿瘤球体的体积。最后，Tripalm-NPs-PTX 降低了源自乳腺癌和肺癌细胞的癌症干细胞（CSCs）的 PTX IC（MCF7 和 A549 CSCs 分别为 6.7 倍和 14.9 倍）。这些结果提供了一种基于使用三棕榈酸甘油酯的新的 PTX 纳米制剂，该制剂提高了 PTX 的抗肿瘤活性，并且可以作为乳腺癌和肺癌治疗中 PTX 递药系统的替代物。
