材料科学
巨噬细胞极化
肿瘤微环境
癌症研究
免疫疗法
聚苯胺
细胞毒性T细胞
生物物理学
内吞作用
免疫系统
巨噬细胞
细胞
生物
免疫学
聚合
生物化学
聚合物
体外
复合材料
作者
Wen Su,Li-Chan Chang,Wei-How Song,Li‐Xing Yang,Liu-Chun Wang,Zi‐Chun Chia,Yu‐Cheng Chin,Yan-Shen Shan,Chih‐Chia Huang,Chen‐Sheng Yeh
标识
DOI:10.1021/acsami.2c03839
摘要
Lung cancer is considered among the deadliest cancers with a poor prognosis. Au@PG nanoparticles (NPs) are gold (Au)-based NPs featuring a polyaniline-based glyco structure (PG) generated from the polymerization of ortho-nitrophenyl-β-d-galactopyranoside (ONPG) with promising M1 macrophage polarization activity, resulting in tumor remodeling and from a cold to a hot microenvironment, which promotes the cytotoxic T cell response and tumor inhibition. The combination of Au@PG NPs and anti-programmed cell death protein 1 (PD-1) therapy improved tumor inhibition and immunosuppression, accompanied by the secretion of immunogenic cytokines. A one-pot synthetic method was developed to achieve glyco-condensation during the formation of Au@PG NPs, which induced macrophage polarization more efficiently than Au@glucose, Au@mannose, and Au@galactose NPs. The switch from M2 to M1 macrophages was dependent on NP size, with smaller Au@PG NPs performing better than larger ones, with effectiveness ranked as follows: 32.2 nm ≈ 29.8 nm < 26.4 nm < 18.3 nm. Cellular uptake by endocytosis induced size-dependent endoplasmic reticulum (ER) stress, which resulted in the activation of spleen tyrosine kinase (SYK), leading to immune modulations and macrophage polarization. Our results suggested the promising potential of Au@PG NPs in lung cancer immunotherapy.
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