Breast cancer, a pervasive malignancy affecting women, demands a diverse treatment approach including chemotherapy, radiotherapy, and surgical interventions. However, the effectiveness of doxorubicin (DOX), a cornerstone in breast cancer therapy, is limited when used as a monotherapy, and concerns about cardiotoxicity persist. Ginsenoside Rg3, a classic compound of traditional Chinese medicine found in Panax ginseng C. A. Mey., possesses diverse pharmacological properties, including cardiovascular protection, immune modulation, and anticancer effects. Ginsenoside Rg3 is considered a promising candidate for enhancing cancer treatment when combined with chemotherapy agents. Nevertheless, the intrinsic challenges of Rg3, such as its poor water solubility and low oral bioavailability, necessitate innovative solutions. Herein, we developed Rg3-PLGA@TMVs by encapsulating Rg3 within PLGA nanoparticles (Rg3-PLGA) and coating them with membranes derived from tumor cell-derived microvesicles (TMVs). Rg3-PLGA@TMVs displayed an array of favorable advantages, including controlled release, prolonged storage stability, high drug loading efficiency and a remarkable ability to activate dendritic cells in vitro. This activation is evident through the augmentation of CD86⁺CD80⁺ dendritic cells, along with a reduction in phagocytic activity and acid phosphatase levels. When combined with DOX, the synergistic effect of Rg3-PLGA@TMVs significantly inhibits 4T1 tumor growth and fosters the development of antitumor immunity in tumor-bearing mice. Most notably, this delivery system effectively mitigates the toxic side effects of DOX, particularly those affecting the heart. Overall, Rg3-PLGA@TMVs provide a novel strategy to enhance the efficacy of DOX while simultaneously mitigating its associated toxicities and demonstrate promising potential for the combined chemo-immunotherapy of breast cancer.

中文翻译：

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仿生人参皂苷 Rg3 PLGA 纳米颗粒包覆肿瘤源微泡可提高化疗疗效并减轻毒性

乳腺癌是一种影响女性的普遍恶性肿瘤，需要多种治疗方法，包括化疗、放疗和手术干预。然而，作为乳腺癌治疗基石的阿霉素 (DOX) 作为单一疗法使用时的有效性有限，而且对心脏毒性的担忧仍然存在。人参皂苷 Rg3 是从人参中发现的经典中药化合物，具有多种药理特性，包括心血管保护、免疫调节和抗癌作用。人参皂苷 Rg3 被认为是与化疗药物联合使用时增强癌症治疗的有希望的候选者。然而，Rg3 的内在挑战，例如水溶性差和口服生物利用度低，需要创新的解决方案。在此，我们通过将 Rg3 封装在 PLGA 纳米粒子（Rg3-PLGA）中并用肿瘤细胞衍生的微泡（TMV）衍生的膜涂覆它们来开发 Rg3-PLGA@TMV。 Rg3-PLGA@TMVs表现出一系列有利的优点，包括控释、长期储存稳定性、高载药效率和体外激活树突状细胞的显着能力。这种激活通过 CD86 ⁺ CD80 ⁺树突状细胞的增加以及吞噬细胞活性和酸性磷酸酶水平的降低而显而易见。当与 DOX 结合时，Rg3-PLGA@TMV 的协同作用可显着抑制 4T1 肿瘤生长，并促进荷瘤小鼠抗肿瘤免疫的发展。最值得注意的是，这种输送系统有效减轻了 DOX 的毒副作用，特别是影响心脏的毒副作用。总体而言，Rg3-PLGA@TMV 提供了一种新的策略来增强 DOX 的功效，同时减轻其相关毒性，并显示出乳腺癌化疗免疫联合治疗的巨大潜力。