Near-Infrared-II Light Induced Mild Hyperthermia Activate Cisplatin-Artemisinin Nanoparticle for Enhanced Chemo/Chemodynamic Therapy and Immunotherapy.

Chemodynamic therapy (CDT) is an effective cancer treatment that uses Fenton reaction to induce cancer cell death. Current clinical applications of CDT are limited by the dependency of external supply of metal ions as well as low catalytic efficiency. Here, a highly efficient metal-free CDT by using endoperoxide bridge-containing artesunate as free radical-generating substance is developed. A Pt(IV) prodrug (A-Pt) containing two artesunate molecules in the axial direction is synthesized, which can be decomposed into cisplatin and artesunate under reducing intracellular environment in tumor cells. To improve the catalytic efficiency for Fenton reaction, a near-infrared-II (NIR-II) photothermal agent IR1048 is incorporated to achieve a mild hyperthermia effect. By encapsulating the A-Pt and IR1048 with human serum albumin, A-Pt-IR NP are formulated for efficient drug delivery in 4T1 tumor-bearing mice. NIR-II light irradiation of A-Pt-IR NP treated mice show accelerated Fenton reaction. In addition, A-Pt-IR NP could also induce strong immunogenic cell death, which effectively reverses the immunosuppressive tumor microenvironment, and augments antitumor immunity. This study demonstrates that A-Pt-IR NP are potent biodegradable NIR-II active chemotherapy/CDT nanomedicine for clinical translation.

Huangqi-Danshen decoction alleviates diabetic nephropathy in db/db mice by inhibiting PINK1/Parkin-mediated mitophagy.

Huangqi-Danshen decoction (HDD) is composed of Astragali Radix (Huang-qi) and Salviae Miltiorrhizae Radix et Rhizoma (Dan-shen), both of which are the most commonly used herbs for the clinical treatment of diabetic nephropathy (DN) in traditional Chinese medicine and show good efficacy. However, the underlying mechanism of this effect is unclear. The aim of this study was to evaluate the effect and potential mechanism of HDD in the treatment of DN in a type 2 diabetic animal model, db/db mice. HDD extract was administered orally to db/db mice at a dose of 6.8 g/kg/day for 12 weeks. At the end of the study, serum, urine, and kidney samples were collected for biochemical and pathological examination. The expression of proteins associated with mitochondrial fission and mitophagy was determined by quantitative real-time PCR, Western blotting, and immunohistochemical analysis. The results showed that treatment with HDD substantially reduced urinary albumin excretion and improved renal injury in db/db mice. Moreover, mitochondrial fission was increased in the kidneys of the db/db mice, as evidenced by enhanced expression of dynamin-related protein 1 and mitochondrial morphological changes. Furthermore, PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy was activated in the db/db mice, which manifested as increased protein expression and obvious autophagic vacuole encapsulating mitochondria. HDD treatment significantly reversed the enhanced mitochondrial fission and PINK1/Parkin-mediated mitophagy in the db/db mice. In conclusion, this work suggested that HDD could protect against type 2 diabetes-induced kidney injury possibly by inhibiting PINK1/Parkin-mediated mitophagy.