将化疗药物与生物活性天然产物结合是一种吸引人的抗癌治疗模式，可以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也有助于对抗癌细胞对药物的耐药性发展。纳米颗粒（NP）介导的药物输送可以通过在体内实现被动和/或主动靶向肿瘤组织进一步改善细胞毒性药物的治疗指数。以阿霉素（DOX）作为模型化疗药物，我们开发了三种基于聚槲皮素（pQCT）的纳米颗粒制剂，这是一种新兴的纳米载体平台。纳米颗粒与DOX、pQCT和Pluronic 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。对纳米颗粒进行物理化学表征结果显示，它们具有球形形态、高单一性，具有良好的药物负载能力和持续的药物释放性能。然后，在体外评估了这些纳米颗粒，以确定其与生物活性天然产物姜黄素（CUR）、丹宁酸（TA）和金盏花酮（TQ）对乳腺癌细胞（MCF-7和MDA-MB-231）进行联合应用时的协同作用。令人惊讶的是，大多数组合都表现出拮抗作用。然而，含有CUR的组合表现出更强的促凋亡效果，与单一药物相比，聚合物修饰的pQCT纳米颗粒呈现出一种增强DOX促进癌细胞凋亡能力的有前景的纳米载体平台。我们的研究结果为pQCT在纳米医学中的潜在应用提供了洞察，同时揭示了生物活性天然产物与DOX自由剂和纳米颗粒制剂联合应用在乳腺癌治疗中的潜力。版权所有 © 2023 Elsevier B.V.。

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.Copyright © 2023. Published by Elsevier B.V.