PDF(Pubmed)
Abstract：
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.
摘要：
相当多的注意力已经集中在探索miR-155在癌症免疫疗法领域的潜在功效。在树突状细胞（DC）中miR-155的水平升高已被证明可以增强其成熟，迁移,细胞因子分泌，以及它们促进T细胞活化的能力。此外,M2巨噬细胞中mir155的过表达增强了向M1表型的极化。相反，miR-155具有在肿瘤组织中诱导免疫抑制细胞如调节性T细胞(Tregs)和骨髓来源的抑制细胞(MDSC)的积累的倾向。为了解释这种差异，必须从能够处理免疫抑制作用的药物中获得帮助。姜黄素（CUR）表现出提示Tregs转化为T辅助1细胞的能力，促进M2肿瘤相关巨噬细胞向M1表型的极化，并阻碍肿瘤微环境中MDSCs的募集和聚集。尽管如此，已知CUR通过阻碍成熟标志物的表达对DC发挥免疫抑制作用。细胞因子,和趋化因子，从而防止DC对免疫刺激剂的应答。因此，设计了一种活性氧/谷胱甘肽双重响应药物输送平台（CUR/miR155@DssD-HbNP），用于共同递送CUR和miR155，目的是探索它们在支持持续和强大的抗肿瘤免疫反应方面的协同潜力。体外和体内实验结果表明，CUR/miR155@DssD-HbNPs可以有效抑制4T1和B16F10肿瘤细胞的活力，触发与损伤相关的分子模式的释放，刺激DCs成熟，随后激活CD8+T细胞，减少免疫抑制细胞群体(MDSCs，Tregs,M2TAM和耗尽的T细胞），促进长期免疫的形成，减少肺部转移性结节的形成。总之,整合CUR和miR155(CUR/miR155@DssD-HbNP)的联合给药系统有望成为黑色素瘤和三阴性乳腺癌免疫治疗的一种有前景的策略.
