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

Abstract

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.

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

“…The gold (Au)-based Au@PG NPs lead to tumor remodeling by switching the TME from cold to hot, thus contributing to the CTL response and tumor suppression without significant cytotoxicity. These results support the potential of Au@PG NPs in lung cancer immunotherapy [39] . In addition, toll-like receptor (TLR) 3 agonists, such as polyriboinosinic-polyribocytidylic acid (poly [I:C]), are reportedly emerging as immunotherapy adjuvants for cancer [40] .…”

“…Mechanistically, macrophages expressing the macrophage receptor with collagenous structure facilitate Treg proliferation and IL-10 production, reduce CD8 + T cell activities, and block NK cell activation, [38] thus providing opportunities for M1 TAM-polarized cancer immunotherapy. For instance, the gold (Au)-based Au@PG NPs exhibit an M1 macrophage phenotype, accompanied by immunogenic cytokine release (reduced levels of immunosuppressive IL-4, IL-10, and IL-13, and increased levels of immunogenic IL-12, IFN-γ, and TNF-α) [39] . The gold (Au)-based Au@PG NPs lead to tumor remodeling by switching the TME from cold to hot, thus contributing to the CTL response and tumor suppression without significant cytotoxicity.…”

Mechanisms of drug resistance to immune checkpoint inhibitors in non-small cell lung cancer

“…In addition, there are many novel drugs for combination therapy, such as targeted therapies ( 207 – 210 ), lysing viruses ( 211 ), cancer vaccines ( 212 ), Chinese herbal medicine ( 213 , 214 ), and nanoparticles ( 215 , 216 ). Meanwhile, metabolism and microbiome with immunotherapy is ongoing.…”

Nanomedicine in Lung Cancer Immunotherapy

“…Su et al demonstrated the potential of Au@PG nanoparticles consisting of Au and polyaniline-based glyco structures. Employing Au@PG nanoparticles in lung cancer immunotherapy resulted in the promising polarization activity of M1 macrophage and the promotion of the cytotoxic T cell response as well as tumor inhibition and the secretion of immunogenic cytokines when combined with PD-1 therapy (Su et al, 2022). Another active targeted nanoparticle is SGT-53 which is capable of restoring the function of the p53 protein and improving anti-PD-1 immunotherapy by delivering the TP53 tumor suppressor gene…”