Jiangsu Key Laboratory of Phylogenomics and Comparative Genomics, Jiangsu Joint International Center of Genomics, School of Life Sciences, Jiangsu Normal University, Xuzhou, 221116, Jiangsu Province, China.
Department of Urology, Xuzhou Central Hospital, Xuzhou, 221009, China.
Biomater Sci. 2023 Jul 25;11(15):5337-5346. doi: 10.1039/d3bm00416c.
Nanomaterials have been identified as a potential therapeutic option for targeting myeloid-derived suppressor cells (MDSCs), which are known to play a crucial role in tumor metastasis and treatment resistance. Here, we report a unique immunologically active nanomaterial composed of ferumoxytol and poly(I : C) (FP-NPs) and investigate its immunoregulatory activities on MDSCs in metastatic melanoma. assays demonstrated that FP-NPs had the ability to significantly impede the progression of metastatic melanoma and decrease the MDSC population in the lungs, spleen, and bone marrow of mice. Both and experiments revealed that FP-NPs reduced the number of granulocytic MDSCs and promoted the differentiation of monocytic MDSCs into anti-tumor M1 macrophages. Transcriptome sequencing indicated that FP-NPs significantly altered the expression of several genes involved in immunity. Analysis of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and quantitative real-time PCR revealed that FP-NPs significantly increased the expression of the myeloid cell differentiation-related gene interferon regulatory factor 7 and activated interferon beta-related signaling pathways, which stimulated the differentiation of MDSCs into M1 macrophages. These findings suggest that FP-NPs, a unique nanomaterial with immunological properties, can induce MDSCs to differentiate into M1 macrophages, potentially offering new treatment prospects for metastatic melanoma in the future.
纳米材料已被确定为一种有潜力的治疗方法，可用于靶向髓系来源的抑制细胞（MDSCs），这些细胞已知在肿瘤转移和治疗耐药中发挥关键作用。在这里，我们报告了一种由 Ferumoxytol 和聚（I：C）组成的独特免疫活性纳米材料（FP-NPs），并研究了其对转移性黑色素瘤中 MDSCs 的免疫调节作用。体内实验表明，FP-NPs 能够显著抑制转移性黑色素瘤的进展，并减少小鼠肺部、脾脏和骨髓中的 MDSC 群体。体内和体外实验均表明，FP-NPs 减少了粒细胞 MDSC 的数量，并促进单核细胞 MDSC 向抗肿瘤 M1 巨噬细胞分化。转录组测序表明，FP-NPs 显著改变了几个与免疫相关的基因的表达。基因本体论、京都基因与基因组百科全书和实时定量 PCR 分析表明，FP-NPs 显著增加了与髓样细胞分化相关的基因干扰素调节因子 7 的表达，并激活了干扰素 β 相关信号通路，从而刺激 MDSC 向 M1 巨噬细胞分化。这些发现表明，FP-NPs 作为一种具有免疫特性的独特纳米材料，可诱导 MDSC 向 M1 巨噬细胞分化，为未来转移性黑色素瘤的治疗提供了新的前景。
