Rationally designed combination nano-therapy approaches have emerged as a promising strategy for resistant breast cancer treatment. This research reports the combination of Docetaxel (DTX) and Thymoquinone (THQ) co-encapsulated within long circulating sub-100 nm mPEG-DSPE-Vitamin E TPGS-Lipid nanocapsules (DxTq-LNCs). DxTq-LNCs with sufficient drug loading exhibited controlled drug release, enhanced protein binding resistance (confirming its long circulation in physiological environment and suitability for iv application) and retained the antioxidant effects of THQ. DxTq-LNCs were further subjected to cytotoxicity analysis against human breast cancer cells (MCF-7 & MDA-MB-231). The presence of multidrug resistance (MDR) reversal agents; Vitamin E TPGS and THQ, along with the nanoencapsulation, re-sensitized the resistant triple negative breast cancer (TNBC) cells to the anticancer effects of DTX. Greater inhibition of cell migration indicated improved anti-metastatic effects. Drastic changes in cellular morphology indicated by nuclear fragmentation (the hall marks of apoptosis), were observed upon DxTq-LNCs treatment to the breast cancer cells. In vivo toxicity studies indicated no substantial blood biochemical and histological changes with near normal appearance of kidney and liver tissue sections upon DxTq-LNCs treatment in contrast to free drug that showed parenchymal degeneration, areas of interstitial haemorrhage, glomerular atrophy and other histological changes, indicating hepato- and nephro-protective potential of DxTq-LNCs. Furthermore, enhanced antitumor efficacy was observed with DxTq-LNCs treatment to mice bearing ehrlich ascites carcinoma. Thus, nanocapsules presents a simple yet effective approach for successful combination chemotherapy with reduced unwanted toxicity.

中文翻译：

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多西紫杉醇和胸腺醌在用于乳腺癌治疗的mPEG-DSPE-维生素E TPGS-脂质纳米胶囊中的共封装：配方优化及其对细胞和体内毒性的影响。

合理设计的组合纳米治疗方法已成为抗药性乳腺癌治疗的一种有前途的策略。这项研究报告了将多西他赛（DTX）和胸腺嘧啶（THQ）联合包裹在长循环的100 nm以下mPEG-DSPE-维生素E TPGS-脂质纳米胶囊（DxTq-LNCs）中。具有足够载药量的DxTq-LNCs表现出受控的药物释放，增强的蛋白结合抗性（确认其在生理环境中的长循环性和适用于静脉内应用）并保留了THQ的抗氧化作用。DxTq-LNCs进一步针对人乳腺癌细胞（MCF-7和MDA-MB-231）进行了细胞毒性分析。多重耐药性逆转剂的存在；维生素E TPGS和THQ，以及纳米胶囊，重新使耐药性三阴性乳腺癌（TNBC）细胞对DTX的抗癌作用敏感。对细胞迁移的更大抑制表明改善的抗转移作用。在对乳腺癌细胞进行DxTq-LNCs治疗后，观察到了核碎裂（细胞凋亡的标志）所指示的细胞形态的急剧变化。体内毒性研究表明，DxTq-LNCs治疗后肾脏和肝脏组织切片几乎正常外观，血液生化和组织学无明显变化，而游离药物则表现出实质性变性，间质性出血，肾小球萎缩和其他组织学变化，这表明DxTq-LNCs的肝和肾保护潜力。此外，DxTq-LNCs治疗对携带埃里希腹水癌的小鼠具有增强的抗肿瘤功效。因此，纳米胶囊为成功的联合化疗提供了简单而有效的方法，同时减少了有害的毒性。