Sunoqrot Suhair, Abusulieh Samah, Abusara Osama H
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
Int J Pharm. 2023 Oct 15;645:123392. doi: 10.1016/j.ijpharm.2023.123392. Epub 2023 Sep 6.
Combining chemotherapeutic agents with bioactive natural products is an attractive cancer treatment modality to reduce the dose and side effects of chemotherapy. Combination treatments with drugs having different mechanisms of action can also be beneficial in combatting the development of drug resistance by cancer cells. Nanoparticle (NP)-mediated drug delivery can further improve the therapeutic index of cytotoxic agents by enabling passive and/or active targeting to tumor tissues in vivo. Using doxorubicin (DOX) as a model chemotherapeutic agent, we developed three NP formulations based on polyquercetin (pQCT), an emerging nanocarrier platform. The NPs were co-assembled with DOX, pQCT, and either Pluronic P123, methoxy poly(ethylene glycol)-amine, or D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS). Physicochemical characterization of the NPs revealed them to have a spherical morphology with high monodispersity, excellent drug loading capacity, and sustained drug release. Then, the NPs were evaluated in vitro to determine their potential synergism when combined with the bioactive natural products curcumin (CUR), tannic acid (TA), and thymoquinone (TQ) against breast cancer cells (MCF-7 and MDA-MB-231). Surprisingly, most of the combinations were found to be antagonistic. However, combinations containing CUR exhibited greater pro-apoptotic effects compared to the single agents, with polymer-modified pQCT NPs presenting as a promising nanoplatform for enhancing DOX's ability to promote cancer cell apoptosis. Our findings provide insights into the potential application of pQCT in nanomedicine, as well as the use of bioactive natural products in combination with DOX as a free agent and as an NP formulation in the treatment of breast cancer.
将化疗药物与生物活性天然产物联合使用是一种颇具吸引力的癌症治疗方式，可降低化疗药物的剂量和副作用。使用具有不同作用机制的药物进行联合治疗，在对抗癌细胞耐药性的发展方面也可能有益。纳米颗粒（NP）介导的药物递送可通过实现体内对肿瘤组织的被动和/或主动靶向，进一步提高细胞毒性药物的治疗指数。以阿霉素（DOX）作为模型化疗药物，我们基于聚槲皮素（pQCT）这一新兴的纳米载体平台开发了三种NP制剂。这些NP与DOX、pQCT以及普朗尼克P123、甲氧基聚（乙二醇）-胺或D-α-生育酚聚（乙二醇）1000琥珀酸酯（TPGS）共同组装。对NP的物理化学表征显示，它们具有球形形态、高单分散性、出色的载药能力和持续的药物释放。然后，对NP进行体外评估，以确定它们与生物活性天然产物姜黄素（CUR）、鞣酸（TA）和百里醌（TQ）联合使用时对乳腺癌细胞（MCF-7和MDA-MB-231）的潜在协同作用。令人惊讶的是，大多数组合被发现具有拮抗作用。然而，与单一药物相比，含有CUR的组合表现出更大的促凋亡作用，聚合物修饰的pQCT NPs呈现为一种有前景的纳米平台，可增强DOX促进癌细胞凋亡的能力。我们的研究结果为pQCT在纳米医学中的潜在应用，以及生物活性天然产物与游离DOX和NP制剂联合用于治疗乳腺癌提供了见解。
