文献：

Nanoparticle‑Loaded Polarized‑Macrophages for Enhanced Tumor Targeting and Cell‑Chemotherapy

文献链接：

https://link.springer.com/article/10.1007/s40820-020-00531-0

作者：

Teng Hou, Tianqi Wang, Weiwei Mu, Rui Yang, Shuang Liang, Zipeng Zhang, Shunli Fu, Tong Gao, Yongjun Liu & Na Zhang

相关产品：

磷脂-罗丹明B DSPE-RB DSPE-rhodamine B

原文摘要：

Cell therapy is a promising strategy for cancer therapy. However, its therapeutic efficiency remains limited due to the complex and immunosuppressive nature of tumor microenvironments. In this study, the “cell-chemotherapy” strategy was presented to enhance antitumor efficacy. M1-type macrophages, which are therapeutic immune cells with both of immunotherapeutic ability and targeting ability, carried sorafenib (SF)-loaded lipid nanoparticles (M1/SLNPs) were developed. M1-type macrophages were used both as therapeutic tool to provide immunotherapy and as delivery vessel to target deliver SF to tumor tissues for chemotherapy simultaneously. M1-type macrophages were obtained by polarizing macrophages using lipopolysaccharide, and M1/SLNPs were obtained by incubating M1-type macrophages with SLNP. Tumor accumulation of M1/SLNP was increased compared with SLNP (p < 0.01), which proved M1/SLNP could enhance tumor targeting of SF. An increased ratio of M1-type macrophages to M2-type macrophages, and the CD3+CD4+ T cells and CD3+CD8+ T cell quantities in tumor tissues after treatment with M1/SLNP indicated M1/SLNP could relieve the immunosuppressive tumor microenvironments. The tumor volumes in the M1/SLNP group were significantly smaller than those in the SLNP group (p < 0.01), indicating M1/SLNP exhibited enhanced antitumor efficacy. Consequently, M1/SLNP showed great potential as a novel cell-chemotherapeutic strategy combining both cell therapy and targeting chemotherapy. 

M1型巨噬细胞是一种具有靶向能力的免疫细胞，携带（SF）负载的脂质纳米粒子（M1/SLNPs）。M1型巨噬细胞通过使用脂多糖极化巨噬细胞而获得，M1/SLNP通过将M1型巨噬细胞与SLNP孵育而获得。

图为：aM1/SLNP的制备。bM1/SLNP用于靶向传递以增强效果的示意图

制备方法：采用SLNP在M/SLNP或M1/SLNP CLSM和TEM中的稳定性来评价SLNP在M/SLNP或M1/SLNP中的稳定性。将DSPE-罗丹明B和大豆卵磷脂溶解在Tween-80水溶液中（1.5%，w/v）中，其他方法与C6-LNP相似。因此，获得了C6-LNP，其中用罗丹明b快速标记LNP，巨噬细胞在12孔板中培养过夜。将巨噬细胞与LPS（1µg mL−1）孵育24 h，获得m1型巨噬细胞。加入C6-LNPs，与巨噬细胞或m1型巨噬细胞孵育2h。PBS洗涤后，细胞与添加10%胎牛血清的新鲜DMEM培养基中孵育不同的时间（0、4、8、12和24 h）。在预定的时间点，用PBS洗涤细胞，并在CLSM下观察。并在24 h后获得细胞，并在透射电镜下观察。

M1/SLNP的Tumor 积聚较SLNP增加（p < 0.01），证明M1/SLNP能增强SF的Tumor 靶向性。M1/SLNPTreatment后，M1型巨噬细胞与M2型巨噬细胞的比例增加，Tumor 组织中CD3+CD4+T细胞和CD3+CD8+T细胞的数量增加，表明M1/SLNP可以缓解免疫抑制性Tumor 微环境。M1/SLNP组的Tumor 体积明显小于SLNP组（p < 0.01），表明M1/SLNP表现出增强s的抗Tumor 功效。因此，M1/SLNP作为一种结合细胞Treatment和靶向Chemotherapy的新型细胞Chemotherapy策略显示出巨大的潜力。