镶嵌纳米免疫治疗ferumoxytol和poly(I:C)通过增强抗血管生成免疫力抑制黑色素瘤。
The combinational nano-immunotherapy of ferumoxytol and poly(I:C) inhibits melanoma via boosting anti-angiogenic immunity.
发表日期:2023 Jan 25
作者:
Yunuo Zheng, Bo Jiang, Hongmei Guo, Zhonghai Zhang, Bo Chen, Zhengkui Zhang, Shaoyuan Wu, Jiaojiao Zhao
来源:
Nanomedicine
摘要:
血管新生在黑色素瘤的进展和转移中起着关键作用,巨噬细胞的促血管新生作用是目前抗血管新生治疗失败的主要原因之一。在此,开发了一种联合了富马铁和聚(I:C)(富马铁/聚(I:C))的纳米免疫治疗方案,以增强巨噬细胞的抗血管新生活性以抑制黑色素瘤的发展。我们的研究发现富马铁/聚(I:C)是一种高效的抗肿瘤治疗方法,毒性有限。无论是体内还是体外实验都表明该组合成功地阻碍了血管新生。富马铁/聚(I:C)能够降低内皮细胞的存活率,从而阻碍管型的形成,特别是富马铁/聚(I:C)能够将巨噬细胞极化为M1表型,并降低血管内皮生长因子的表达,从而放大了富马铁/聚(I:C)的抗血管新生性能。这种富马铁/聚(I:C)的纳米免疫治疗方案可以丰富富马铁的抗血管新生治疗特性,为黑色素瘤的治疗提供新的思路。版权所有© 2023 Elsevier Inc.保留所有权利。
Angiogenesis plays a key role in the progression and metastasis of melanoma, and the pro-angiogenic effect of macrophages is one major reason for the failure of current anti-angiogenic therapies. Here, a nano-immunotherapy combining ferumoxytol and poly(I:C) (ferumoxytol/poly(I:C)) has been developed to boost the anti-angiogenic activities of macrophages to inhibit melanoma. Our findings demonstrated that ferumoxytol/poly(I:C) was a highly efficacious anti-tumor therapy with limited toxicity. Both in vivo and in vitro experiments indicated that this combination was successful in impeding angiogenesis. Ferumoxytol/poly(I:C) was demonstrated to reduce the viability of endothelial cells, thus hindering tube formation. Particularly, ferumoxytol/poly(I:C) was able to polarize macrophages to the M1 phenotype and decrease the expression of vascular endothelial growth factor, which in turn amplified the anti-angiogenic properties of ferumoxytol/poly(I:C). This combination of ferumoxytol/poly(I:C) nano-immunotherapy enriches the anti-angiogenic therapeutic nature of ferumoxytol and will shed new light on the treatment of melanoma.Copyright © 2023 Elsevier Inc. All rights reserved.