人们对探索 miR-155 在癌症免疫治疗领域的潜在功效给予了极大的关注。树突状细胞 (DC) 中 miR-155 水平升高已被证明可以增强其成熟、迁移、细胞因子分泌以及促进 T 细胞活化的能力。此外，M2 巨噬细胞中 mir155 的过度表达促进了向 M1 表型的极化。相反，miR-155有诱导肿瘤组织中免疫抑制细胞（如调节性T细胞（Treg）和骨髓源性抑制细胞（MDSC））积累的倾向。为了解决这种差异，必须寻求能够应对免疫抑制作用的药物的帮助。姜黄素 (CUR) 能够促使 Tregs 转化为辅助性 T 细胞 1，促进 M2 肿瘤相关巨噬细胞向 M1 表型极化，并阻止肿瘤微环境中 MDSC 的招募和聚集。尽管如此，已知 CUR 通过阻碍成熟标志物、细胞因子和趋化因子的表达对 DC 产生免疫抑制作用，从而阻止 DC 对免疫刺激剂的反应。因此，设计了活性氧/谷胱甘肽双重响应药物输送平台（CUR/miR155@DssD-Hb NPs）来共同递送CUR和miR155，目的是探索它们在支持持续和强大的抗肿瘤方面的协同潜力。免疫反应。体外和体内结果表明，CUR/miR155@DssD-Hb NPs 可以有效抑制 4T1 和 B16F10 肿瘤细胞的活力，触发损伤相关分子模式的释放，刺激 DC 成熟，随后激活 CD8 T 细胞，减少免疫抑制细胞群（MDSC、Tregs、M2 TAM 和耗尽的 T 细胞），促进长期免疫的形成并减少肺部转移结节的形成。总之，整合 CUR 和 miR155 (CUR/miR155@DssD-Hb NPs) 的共传递系统显示出作为黑色素瘤和三阴性乳腺癌免疫治疗的有前途的策略的前景。© 2024。作者。

Considerable attention has been directed towards exploring the potential efficacy of miR-155 in the realm of cancer immunotherapy. Elevated levels of miR-155 in dendritic cells (DCs) have been shown to enhance their maturation, migration, cytokine secretion, and their ability to promote T cell activation. In addition, overexpression of mir155 in M2 macrophages boost the polarization towards the M1 phenotype. Conversely, miR-155 has the propensity to induce the accumulation of immunosuppressive cells like regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in the tumor tissue. To account for this discrepancy, it is imperative to get help from a drug that could deal with immunosuppressive effect. Curcumin (CUR) exhibits the capacity to prompt Tregs converse into T helper 1 cells, fostering the polarization of M2 tumor-associated macrophage towards the M1 phenotype, and impeding the recruitment and aggregation of MDSCs within the tumor microenvironment. Nonetheless, CUR is known to exert an immunosuppressive impact on DCs by hindering the expression of maturation markers, cytokines, and chemokines, thereby prevent DCs response to immunostimulatory agents. Hence, a reactive oxygen species/glutathione dual responsive drug conveyance platform (CUR/miR155@DssD-Hb NPs) was devised to co-deliver CUR and miR155, with the aim of exploring their synergistic potential in bolstering a sustained and robust anti-tumor immune response. In vitro and in vivo results have suggested that CUR/miR155@DssD-Hb NPs can effectively inhibit the viability of 4T1 and B16F10 tumor cells, trigger the release of damage associated molecular patterns, stimulate DCs maturation, subsequent activation of CD8+ T cells, diminish immunosuppressive cell populations (MDSCs, Tregs, M2 TAMs and exhausted T cells), promote the formation of long-term immunity and lessen the formation of metastatic nodules in the lungs. In summary, the co-delivery system integrating CUR and miR155 (CUR/miR155@DssD-Hb NPs) demonstrates promise as a promising strategy for the immunotherapy of melanoma and triple negative breast cancer.© 2024. The Author(s).