Optimized PEGylated paclitaxel and 6-gingerol co-loaded liposomes induce G2/M phase arrest and apoptosis in MDA-MB-231 breast and A549 lung cancer cells

The study aimed to optimize and develop novel PEGylated co-loaded nanoliposome entrapped with paclitaxel (PTX) and 6-gingerol (Gn) (PEG-Lipo-PTX-Gn) by response surface methodology (RSM) approach to prevent the diffusion and resistant-related issues of PTX in oncotherapy. Physiochemical characterization studies results revealed that the prepared PEG-Lipo-PTX-Gn attained optimum particle size, shape, charge, polydispersity index (PDI) as well as showed synergistic entrapment of PTX and Gn, sustained drug release, better colloidal stability and structural integrity. PEG-Lipo-PTX-Gn exhibited a noteworthy antiproliferative effect, apoptotic percentage and a higher proportion of G2/M cell cycle arrest in MDA-MB-231 and A549 cell lines. Meanwhile, no significant toxicity was observed in normal cell lines (HEK 293 kidney embryonic cells and L929 fibroblast cells). Another testament to its efficacy is the dramatic decline in Bcl-2 levels in the PEG-Lipo-PTX-Gn-treated group. Hence, optimized PEG-Lipo-PTX-Gn could be a promising novel approach in cancer treatment regimens.

本研究旨在通过响应面法（response surface methodology, RSM），优化并构建一种新型聚乙二醇化共载紫杉醇（paclitaxel, PTX）与6-姜酚（6-gingerol, Gn）的纳米脂质体（PEG-Lipo-PTX-Gn），以解决紫杉醇在肿瘤治疗中易出现的扩散及耐药性问题。理化表征研究结果表明，所制备的PEG-Lipo-PTX-Gn具备最优的粒径、形貌、表面电荷及多分散指数（polydispersity index, PDI），可实现PTX与Gn的协同包载，同时展现出优异的缓释释药性能、良好的胶体稳定性与结构完整性。PEG-Lipo-PTX-Gn在MDA-MB-231乳腺癌细胞系与A549肺癌细胞系中，表现出显著的抗增殖作用、更高的凋亡率以及G2/M期细胞周期阻滞比例。与此同时，该制剂在正常细胞系（HEK 293胚肾细胞与L929成纤维细胞）中未观察到明显毒性。另一项验证其疗效的证据是，经PEG-Lipo-PTX-Gn处理的组别中，B细胞淋巴瘤-2蛋白（Bcl-2）的表达水平出现显著下降。综上，优化后的PEG-Lipo-PTX-Gn有望成为肿瘤治疗方案中极具潜力的新型策略。