The tumor microenvironment (TME) is enriched with immunosuppressive factors that inhibit the recruitment and activation of dendritic cells (DCs), thereby reducing the efficacy of tumor immunotherapy. To address this challenge, we propose an innovative strategy involving the sequential administration of MCM magnetic nanoparticles carrying PROTAC drugs (MCM/ARV) and M-BMDCs in the TEM. This approach not only replenishes DCs in the TEM, but also increases antigen uptake through the attraction between the magnetic particles and promotes DC activation and antigen presentation, thus continuously enhancing the tumor immune cycle. MCM nanoparticles (magnetic nanoclusters coated with calcium-doped manganese carbonate) efficiently load the tumor-targeting drug PROTAC (ARV-825), enhancing its bioavailability, leading to specific degradation of BRD4 in tumor cells, and releasing a large number of tumor-associated antigens. These antigens were captured by MCM nanoparticles to construct magnetized tumor vaccines. Magnetic M-BMDCs introduced at the tumor site are attracted to these magnetized vaccines, resulting in a significant increase in antigen uptake and activation of DCs, significantly enhancing the tumor immune cycle. This co-administration strategy of magnetized vaccines and magnetized BMDCs provides a unique combination therapy for reversing immunosuppressive TEM and enhancing the efficacy of tumor immunotherapy.

中文翻译：

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通过癌症免疫循环回路构建用于癌症免疫治疗的新型磁性系统


肿瘤微环境 （TME） 富含免疫抑制因子，可抑制树突状细胞 （DC） 的募集和活化，从而降低肿瘤免疫治疗的疗效。为了应对这一挑战，我们提出了一种创新策略，涉及在 TEM 中连续施用携带 PROTAC 药物 （MCM/ARV） 和 M-BMDC 的 MCM 磁性纳米颗粒。这种方法不仅可以补充 TEM 中的 DC，还可以通过磁性颗粒之间的吸引力增加抗原摄取，促进 DC 激活和抗原呈递，从而不断增强肿瘤免疫周期。MCM 纳米颗粒（涂有掺钙碳酸锰的磁性纳米簇）有效地加载肿瘤靶向药物 PROTAC （ARV-825），增强其生物利用度，导致肿瘤细胞中 BRD4 的特异性降解，并释放大量肿瘤相关抗原。这些抗原被 MCM 纳米颗粒捕获以构建磁化肿瘤疫苗。引入肿瘤部位的磁性 M-BMDC 被这些磁化疫苗吸引，导致 DC 的抗原摄取和激活显着增加，显着增强肿瘤免疫周期。磁化疫苗和磁化 BMDC 的这种联合给药策略为逆转免疫抑制 TEM 和增强肿瘤免疫疗法的疗效提供了一种独特的联合疗法。