Chitosan-Poly(Acrylic Acid) Nanoparticles Loaded with R848 and MnCl(2) Inhibit Melanoma via Regulating Macrophage Polarization and Dendritic Cell Maturation.
Chitosan-Poly(Acrylic Acid) Nanoparticles Loaded with R848 and MnCl(2) Inhibit Melanoma via Regulating Macrophage Polarization and Dendritic Cell Maturation.
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负载 R848 和 MnCl2 的壳聚糖聚丙烯酸纳米粒子通过调节巨噬细胞极化和树突状细胞成熟抑制黑色素瘤
DOI：
10.2147/ijn.s318363
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发表时间：
2021
影响因子：
8
通讯作者：
Zhao S
中科院分区：
文献类型：
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作者：
Liu X;Xu Y;Yin L;Hou Y;Zhao S
由于肿瘤微环境（TME）中的免疫力会影响肿瘤的发展和进展，因此调节免疫细胞的策略被认为具有重要的治疗作用。据报道，MN2+强烈促进了抗原呈递细胞（APC）的成熟，从而增强了CD8+ T细胞的细胞毒性。装有R848和MNCL2（R-M@CS-PAA NP）可以通过调节免疫细胞的功能来执行抗肿瘤效应。
制备了R-M@CS-PAA NP，并在体外和体内探索了它们的基本特征，抗肿瘤效应和潜在机制。
R-M@CS-PAA NP在B16F10小鼠黑色素瘤模型中轻松释放MNCL2和R848，R-M@CS-PAA NPS与对照组相比，执行了最重要的抗黑色素瘤效应单独显示了FITC标记的R-M@CS-PAA NP，在R-M@CS-PAA NP中积累了大量的肿瘤。此外，在体外实验表明，R-M@CS-PAA NPS极化巨噬细胞抑制B16F10细胞的增殖，也可以增强CD8+ T细胞的杀伤功能@CS-PAA NP不仅通过STING和NF-limb途径促进了APC（例如树突状细胞和巨噬细胞）的成熟，而且还增强了树突细胞对Ovalbumin呈现Ovalbumin对OT-I CD8+ T细胞的能力，从-i CD8+ T细胞对表达卵蛋白的B16F10细胞。
这些数据表明，R-M@CS-PAA NP的给药是针对黑色素瘤的有效治疗策略。
Purpose Since immune cells in the tumor microenvironment (TME) can affect the development and progression of tumors, strategies modulating immune cells are considered to have an important therapeutic effect. As a TLR7/8 agonist, R848 effectively activates the innate immune cells to exert an anti-tumor effect. Mn2+ has been reported to strongly promote the maturation of antigen-presenting cells (APCs), thereby enhancing the cytotoxicity of CD8+ T cells. Thus, we tried to investigate whether chitosan-poly(acrylic acid) nanoparticles (CS-PAA NPs) loaded with R848 and MnCl2 (R-M@CS-PAA NPs) could exert an anti-tumor effect by regulating the function of immune cells. Methods R-M@CS-PAA NPs were prepared, and their basic characteristics, anti-tumor effect, and potential mechanisms were explored both in vitro and in vivo. Results R-M@CS-PAA NPs easily released MnCl2 and R848 at low pH. In B16F10 mouse melanoma model, R-M@CS-PAA NPs exerted the most significant anti-melanoma effect compared with the control group and CS-PAA NPs loaded with R848 or MnCl2 alone. FITC-labeled R-M@CS-PAA NPs were displayed to be accumulated at the tumor site. R-M@CS-PAA NPs significantly increased the infiltration of M1 macrophages and CD8+ T cells but reduced the number of suppressive immune cells in the TME. Moreover, in vitro experiments showed that R-M@CS-PAA NPs polarized macrophages into the M1 phenotype to inhibit the proliferation of B16F10 cells. R-M@CS-PAA NPs also enhanced the killing function of CD8+ T cells to B16F10 cells. Of note, R-M@CS-PAA NPs not only promoted the maturation of APCs such as dendritic cells and macrophages by STING and NF-кB pathways, but also enhanced the ability of dendritic cells to present ovalbumin to OT-I CD8+ T cells to enhance the cytotoxicity of OT-I CD8+ T cells to ovalbumin-expressing B16F10 cells. Conclusion These data indicate that the administration of R-M@CS-PAA NPs is an effective therapeutic strategy against melanoma.