Near-Infrared-II-Activatable Self-Assembled Manganese Porphyrin-Gold Heterostructures for Photoacoustic Imaging-Guided Sonodynamic-Augmented Photothermal/Photodynamic Therapy.

Porphyrins and their derivatives are widely used as photosensitizers and sonosensitizers in tumor treatment. Nevertheless, their poor water solubility and low chemical stability reduce their singlet oxygen (1O2) yield and, consequently, their photodynamic therapy (PDT) and sonodynamic therapy (SDT) efficiency. Although strategies for porphyrin molecule assembly have been developed to augment 1O2 generation, there is scope for further improving PDT and SDT efficiencies. Herein, we synthesized ordered manganese porphyrin (SM) nanoparticles with well-defined self-assembled metalloporphyrin networks that enabled efficient energy transfer for enhanced photocatalytic and sonocatalytic activity in 1O2 production. Subsequently, Au nanoparticles were grown in situ on the SM surface by anchoring the terminal alkynyl of porphyrin to form plasmonic SMA heterostructures, which showed the excellent near-infrared-II (NIR-II) region absorption and photothermal properties, and facilitated electron-hole pair separation and transfer. With the modification of hyaluronic acid (HA), SMAH heterostructure nanocomposites exhibited good water solubility and were actively targeted to cancer cells. Under NIR-II light and ultrasound (US) irradiation, the SMAH generates hyperthermia, and a large amount of 1O2, inducing cancer cell damage. Both in vitro and in vivo studies confirmed that the SMAH nanocomposites effectively suppressed tumor growth by decreasing GSH levels in SDT-augmented PDT/PTT. Moreover, by utilizing the strong absorption in the NIR-II window, SMAH nanocomposites can achieve NIR-II photoacoustic imaging-guided combined cancer treatment. This work provides a paradigm for enhancing the 1O2 yield of metalloporphyrins to improve the synergistic therapeutic effect of SDT/PDT/PTT.

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 CeO2-x@HA Nanotheranostics for Photoacoustic Imaging-Guided Sonodynamic-Enhanced Synergistic Phototherapy.

The therapeutic effect of photothermal therapy (PTT) and photodynamic therapy (PDT) is severely limited because of the shallow tissue penetration depth of the first near-infrared (NIR-I) light. Multifunctional nanotheranostics irradiated by the second near-infrared (NIR-II) light have received wide interest with respect to deeper tissue penetration, and sonodynamic therapy (SDT) synergistic phototherapy can achieve the complete elimination of tumors. Herein, we successfully constructed a single NIR-II light-induced nanotheranostic using cerium oxide (CeO2-x) with abundant oxygen vacancies for photoacoustic imaging-guided SDT-enhanced phototherapy for the first time. CeO2-x with surface crystalline disorder showed extensive NIR-II region absorption and an outstanding photothermal conversion ability. In addition, the CeO2-x layer with numerous oxygen defects can promote the separation of holes and electrons by ultrasound irradiation, which can remarkably enhance the efficacy of phototherapy to achieve high-efficiency tumor ablation. CeO2-x was surface modified with hyaluronic acid (HA) to prepare CeO2-x@HA to allow active tumor targeting efficiency. Both cell and animal experiments confirmed that all-in-one CeO2-x@HA exhibited a high therapeutic efficacy of SDT-enhanced PDT/PTT under 1064 nm laser irradiation, which achieved complete tumor eradication without systemic toxicity. This study significantly broadened the application of NIR-II-responsive CeO2-x for photoacoustic imaging-mediated SDT-enhanced phototherapy to the highly efficient and precise elimination of tumors.

Correlation between mimecan expression and coronary artery stenosis in patients with coronary heart disease.

OBJECTIVE: This study aimed to investigate the correlation between coronary artery stenosis and Mimecan expression in patients with coronary heart disease (CHD). METHODS: Seventy eight patients with CHD and 80 controls without vascular lesions were recruited into present study. CHD patients were divided into one-vessel CHD subgroup, 2-vessel CHD subgroup and multivessel CHD subgroup. ELISA was performed to detect the expressions of serum Mimecan and nuclear factor kappaB (NF-κB). RESULTS: When compared with control group, the expressions of serum mimecan gene and NF-κB significantly increased in CHD groups (P < 0.05); When compared with one-vessel and two-vessel CHD subgroups, the expressions of serum mimecan and NF-κB significantly increased in multivessel CHD subgroup (P < 0.05), significant difference was observed among three subgroups (P < 0.05). The expressions of serum mimecan and NF-κB were positively related to the severity of coronary lesions (rmimecan=0.79, rNF-κB=0.83, P < 0.05). CONCLUSION: Increased expressions of serum mimecan and NF-κB in CHD patients are related to cardiac insufficiency, which may be ascribed to the binding of NF-κB to mimecan gene.