Polyaniline-Based Glyco-Condensation on Au Nanoparticles Enhances Immunotherapy in Lung Cancer

• DOI: 10.1021/acsami.2c03839
• Publication Date: 2022-05-17T14:12:26Z
• Authors: Wen-Pin 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
• Keywords: 0301 basic medicine; 03 medical and health sciences; Aniline Compounds; Lung Neoplasms; Tumor Microenvironment; Humans; Metal Nanoparticles; Nanoparticles; Gold; Immunotherapy; 3. Good health

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.