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.

Herein, we employ a galvanic replacement approach to create atomically dispersed Au on degradable zero-valent Cu nanocubes for tumor treatments on female mice. Controlling the addition of precursor HAuCl4 allows for the fabrication of different atomic ratios of AuxCuy. X-ray absorption near edge spectra indicates that Au and Cu are the predominant oxidation states of zero valence. This suggests that the charges of Au and Cu remain unchanged after galvanic replacement. Specifically, Au0.02Cu0.98 composition reveals the enhanced •OH generation following O2 → H2O2 → •OH. The degradable Au0.02Cu0.98 released Cu+ and Cu2+ resulting in oxygen reduction and Fenton-like reactions. Simulation studies indicate that Au single atoms boot zero-valent copper to reveal the catalytic capability of Au0.02Cu0.98 for O2 → H2O2 → •OH as well. Instead of using endogenous H2O2, H2O2 can be sourced from the O2 in the air through the use of nanocubes. Notably, the Au0.02Cu0.98 structure is degradable and renal-clearable.

Ineffective site-specific delivery has seriously impeded the efficacy of nanoparticle-based drugs to a disease site. Here, we report the preparation of three different shapes (sphere, scroll, and oblate) to systematically evaluate the impact of the marginative delivery on the efficacy of magnetic resonance (MR) imaging-guided X-ray irradiation at a low dose of 1 Gy. In addition to the shape effect, the therapeutic efficacy is investigated for the first time to be strongly related to the structure effect that is associated with the chemical activity. The enhanced particle–vessel wall interaction of both the flat scroll and oblate following margination dynamics leads to greater accumulation in the lungs, resulting in superior performance over the sphere against lung tumor growth and suppression of lung metastasis. Furthermore, the impact of the structural discrepancy in nanoparticles on therapeutic efficacy is considered. The tetragonal oblate reveals that the feasibility of the charge-transfer process outperforms the orthorhombic scroll and cubic sphere to suppress tumors. Finally, surface area is also a crucial factor affecting the efficacy of X-ray treatments from the as-prepared particles.

Ultrasonic irradiation of liquids can induce catalytic activity in semiconductor nanoparticles (sonocatalysis/sonosensitization) similar to light-induced photocatalysis/photosensitization. However, due to the complexity of the acoustic cavitation processes involved in sonocatalysis/sonosensitization, an ideal nanoparticle design has not been identified for them. Herein, the size-and ligand-dependent ultrasonic activation of thiolate gold nanoclusters (Au NCs) and their photosensitizing and sonosensitizing abilities for singlet oxygen ( 1 O 2 ) generation were investigated. The difference between Au NC-based photosensitization and sonosensitization was also elucidated, along with a mechanism for the latter. For Au 25 NC-based sonosensitization and photosensitization, the ligand effect on the 1 O 2 -generation efficiency was in the order of glutathione < captopril < 4-mercaptobenzoic acid. The competing 1 O 2 production and quenching reactions using sono-/photo-excited Au 25 NCs determined the net 1 O 2 production. The size effects on the 1 O 2 -generation efficiency were in the order of Au 144 ≫ Au 25 > plasmonic Au nanoparticle for sonosensitization, as opposed to the case of photosensitization: Au 25 ≫ Au 144 ∼ plasmonic Au nanoparticle. The 1 O 2 generation via ultrasonically excited Au 144 NCs correlated with high-energy ultrasonic cavitation depending on the ultrasonication power and frequency. Therefore, high-energy ultrasonic cavitation-mediated Au 144 NC-based sonosensitizers could be effectively used in the production of 1 O 2 for various chemical and biomedical applications.