Near-infrared-II-activatable sulfur-deficient plasmonic Bi2S3-x-Au heterostructures for photoacoustic imaging-guided ultrasound enhanced high performance phototherapy.

Bismuth sulfide is widely used as an n-type semiconductor material in photocatalytic reactions. However, bismuth sulfide has poor absorption in the near-infrared region and low charge separation efficiency, limiting its application in phototherapy and sonodynamic therapy (SDT). In this study, we successfully synthesized an "all-in-one" phototheranostic nanoplatform, namely Bi2S3-x-Au@HA, based on a single second near-infrared (NIR-II) light-responsive Schottky-type Bi2S3-x-Au heterostructure for photoacoustic (PA) imaging-guided SDT-enhanced photodynamic therapy (PDT)/photothermal therapy (PTT). Bi2S3-x-Au@HA exhibits excellent NIR-II plasmonic and photothermal properties, rendering it with NIR-II PA imaging capabilities for accurate diagnosis. Additionally, the high-density sulfur vacancies constructed on the Bi2S3 surface cause it to possess a reduced band gap (1.21 eV) that can act as an electron trap. Using the density functional theory, we confirmed that the light and ultrasound-induced electrons are more likely to aggregate on the Au nanoparticle surface through interfacial self-assembly, which promotes electron-hole separation and enhances photocatalytic activity with increased reactive oxygen species (ROS) generation. With a further modification of hyaluronic acid (HA), Bi2S3-x-Au@HA can selectively target cancer cells through HA and CD44 protein interactions. Both in vitro and in vivo experiments demonstrated that Bi2S3-x-Au@HA effectively suppressed tumor growth through SDT-enhanced PTT/PDT under a single NIR-II laser and ultrasound irradiation with negligible toxicity. Our findings provide a framework for fabricating Schottky-type heterostructures as single NIR-II light-responsive nanotheranostic agents for PA imaging-guided cancer phototherapy.

Mechanism of Cytotoxic Action of Gold Nanorods Photothermal Therapy for A549 Cell.

Photothermal therapy has developed into an important field of tumor treatment research, and numerous studies have focused on the preparation of photothermal therapeutic agents, tumor targeting, diagnosis, and treatment integration. However, there are few studies on the mechanism of photothermal therapy acting on cancer cells. Here we investigated the metabolomics of lung cancer cell A549 during gold nanorod (GNR) photothermal treatment by high-resolution LC/MS, and several differential metabolites and corresponding metabolic pathways during photothermal therapy were found. The main differential metabolites contained 18-hydroxyoleate, beta-alanopine and cis-9,10-epoxystearic acid, and phosphorylcholine. Pathway analysis also showed metabolic changes involving cutin, suberine, and wax biosynthesis, pyruvate and glutamic acid synthesis, and choline metabolism. Analysis also showed that the photothermal process of GNRs may induce cytotoxicity by affecting pyruvate and glutamate synthesis, normal choline metabolism, and ultimately apoptosis.

NIR-II-responsive AuNRs@SiO2-RB@MnO2 nanotheranostic for multimodal imaging-guided CDT/PTT synergistic cancer therapy.

Specific tumor-responsive capabilities and efficient synergistic therapeutic performance are the keys to effective tumor treatment. Herein, AuNRs@SiO2-RB@MnO2 was developed as a new type of tumor-responsive nanotheranostic for multimodal imaging and synergistic chemodynamic/photothermal therapy. In AuNRs@SiO2-RB@MnO2, the SiO2 layer wraps the AuNRs, providing light absorption in the second near-infrared (NIR-II) region. The SiO2 layer also adsorbs the MnO2 nanosheets, which have Fenton-like activity, resulting in a fluorescent sensing platform based on the fluorescence quenching properties of MnO2 for rhodamine B dye. The fluorescence can be recovered by the consumption of MnO2 by glutathione, which simultaneously produces Mn2+ in the tumor region. The recovery of fluorescence reflects the consumption of glutathione and the increase in Mn2+, which produces hydroxyl radicals via Fenton-like reaction in the tumor microenvironment to realize chemodynamic therapy. Meanwhile, the AuNRs are a good photothermal reagent that can effectively absorb NIR-II light and convert it into heat energy to kill tumor cells via photothermal therapy. The NIR-II absorption performance of the AuNRs provides good photoacoustic imaging and deep photothermal performance, which is favorable for efficient NIR-II photoacoustic imaging-guided photothermal therapy. As a result, the AuNRs@SiO2-RB@MnO2 nanotheranostic exhibits outstanding imaging and synergistic chemodynamic/photothermal therapeutic performance for tumor imaging and treatment.