Al Saqr Ahmed, Wani Shahid Ud Din, Gangadharappa H V, Aldawsari Mohammed F, Khafagy El-Sayed, Lila Amr S Abu
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-kharj 11942, Saudi Arabia.
Department of Pharmaceutics, CT Institute of Pharmaceutical Sciences, Jalandhar 144020, India.
Polymers (Basel). 2021 Apr 27;13(9):1416. doi: 10.3390/polym13091416.
Despite decades of research, breast cancer therapy remains a great challenge. Docetaxel is an antimicrotubule agent that is effectively used for the treatment of breast cancer. However, its clinical use is significantly hampered by its low water solubility and systemic toxicity. The current study was designed to prepare docetaxel (DXL)-loaded silk-fibroin-based nanoparticles (SF-NPs) and to screen their potential antitumor activity against breast cancer cell lines. DXL-loaded SF-NPs were prepared using a nanoprecipitation technique and were evaluated for particle size, zeta potential, entrapment efficiency, and in vitro release profile. In addition, DXL-loaded SF-NPs were screened for in vitro cytotoxicity, cellular uptake, and apoptotic potential against MCF-7 and MDA-MB-231 breast cancer cell lines. The prepared DXL-loaded SF-NPs were 178 to 198 nm in diameter with a net negative surface charge and entrapment efficiency ranging from 56% to 72%. In vitro release studies exhibited a biphasic release profile of DXL from SF-NPs with sustained drug release for 72 h. In vitro cell studies revealed that entrapment of DXL within SF-NPs significantly improved cytotoxic potential against breast cancer cell lines, compared to the free drug, and enhanced cellular uptake of DXL by breast cancer cells. Furthermore, the accumulation in the G2/M phase was significantly higher in cells treated with DXL-loaded SF-NPs than in cells treated with free DXL. Collectively, the superior antitumor activities of DXL-loaded SF-NPs against breast cancer cells, compared to free DXL, could be ascribed to improved apoptosis and cell cycle arrest. Our results highlighted the feasibility of using silk fibroin nanoparticles as a nontoxic biocompatible delivery vehicle for enhanced therapeutic outcomes in breast cancer.
尽管经过了数十年的研究，乳腺癌治疗仍然是一项巨大的挑战。多西他赛是一种抗微管剂，有效地用于乳腺癌治疗。然而，其低水溶性和全身毒性严重阻碍了它的临床应用。本研究旨在制备负载多西他赛（DXL）的丝素蛋白基纳米颗粒（SF-NPs），并筛选其对乳腺癌细胞系的潜在抗肿瘤活性。采用纳米沉淀技术制备负载DXL的SF-NPs，并对其粒径、zeta电位、包封率和体外释放曲线进行评估。此外，还对负载DXL的SF-NPs进行了体外细胞毒性、细胞摄取以及对MCF-7和MDA-MB-231乳腺癌细胞系的凋亡潜力筛选。所制备的负载DXL的SF-NPs直径为178至198nm，表面带净负电荷，包封率为56%至72%。体外释放研究显示DXL从SF-NPs呈现双相释放曲线，药物持续释放72小时。体外细胞研究表明，与游离药物相比，DXL包封在SF-NPs中显著提高了对乳腺癌细胞系的细胞毒性潜力，并增强了乳腺癌细胞对DXL的摄取。此外，负载DXL的SF-NPs处理的细胞中G2/M期的积累明显高于游离DXL处理的细胞。总体而言，与游离DXL相比，负载DXL的SF-NPs对乳腺癌细胞具有更强的抗肿瘤活性，这可能归因于凋亡的改善和细胞周期阻滞。我们的结果突出了使用丝素蛋白纳米颗粒作为无毒生物相容性递送载体以提高乳腺癌治疗效果的可行性。
