Self-Produced O2 CNs-Based Nanocarriers of DNA Hydrophobization Strategy Triggers Photodynamic and Mitochondrial-Derived Ferroptosis for Hepatocellular Carcinoma Combined Treatment.

Hypoxia can aggravate tumor occurrence, development, invasion, and metastasis, and greatly inhibit the photodynamic therapy (PDT) effect. Herein, carbon nitride (CNs)-based DNA and photosensitizer co-delivery systems (BPSCNs) with oxygen-producing functions are developed to address this problem. Selenide glucose (Seglu) is used as the dopant to prepare red/NIR-active CNs (SegluCNs). The tumor-targeting unit Bio-PEG2000 is utilized to construct BPSCNs nanoparticles through esterification reactions. Furthermore, DNA hydrophobization is realized via mixing P53 gene with a positively charged mitochondrial-targeted near-infrared (NIR) emitting photosensitizer (MTTPY), which is encapsulated in non-cationic BPSCNs for synergistic delivery. Ester bonds in BPSCNs@MTTPY-P53 complexes can be disrupted by lipase in the liver to facilitate P53 release, upregulated P53 expression, and promoted HIF-1α degradation in mitochondria. In addition, the oxygen produced by the complexes improved the hypoxic microenvironment of hepatocellular carcinoma (HCC), synergistically downregulated HIF-1α expression in mitochondria, promoted mitochondrial-derived ferroptosis and enhanced the PDT effect of the MTTPY unit. Both in vivo and in vitro experiments indicated that the transfected P53-DNA, produced O2 and ROS by these complexes synergistically led to mitochondrial-derived ferroptosis in hepatoma cells through the HIF-1α/SLC7A11 pathway, and completely avoiding PDT resistance caused by hypoxia, exerting a significant therapeutic role in HCC treatment.

Highly water-dispersible PCN nanosheets as light-controlled lysosome self-promoting escape type non-cationic gene carriers for tumor therapy.

The construction of non-viral gene delivery faces two major challenges: cytotoxicity caused by high cationic charge units and easy degradation by lysosomes. Herein, highly water-dispersible polymeric carbon nitride (PCN) nanosheets were utilized as the core to construct a light-controlled non-cationic gene delivery system with sufficient lysosomal escape ability. In this system, these nanosheets exhibited efficient DNA condensation, outstanding biocompatibility, transfection tracking, light responsiveness and high transfection efficiency. Once PCN-DNA was taken up by the tumor cells, the accumulated ROS generated by photosensitizers (PSs) under light irradiation would destroy the structure of lysosomes, promote the escape of PCN-DNA and increase the efficiency of gene transfection. Simultaneously, the gene transfection process could be tracked in real time through fluorescence imaging technology, which was conducive to investigate the transfection mechanism. In vitro and in vivo experiments further confirmed that PCN nanosheets loaded with the P53 gene were beneficial to the regeneration of the P53 apoptotic pathway, increased tumor sensitivity to PSs, and further induced tumor cell apoptosis. In summary, the highly water-dispersible PCN nanosheets were applied to light-controlled self-escaping gene delivery for the first time, and tumor gene therapy was successfully realized.

Solid-state synthesis of single-phase nickel monophosphosulfide for the oxygen evolution reaction.

High-performance and cost-effective nonprecious-metal catalysts are essential for the next-generation oxygen evolution reaction (OER). However, the electrocatalysis of the OER during water splitting is often carried out by using noble metal catalysts, such as RuO2 or IrO2 with high-cost and limited stability. Herein, we reported a successful synthesis of a ternary nickel monophosphosulfide (NiPS) compound via a simple solid-state route and further investigated its electrocatalytic performances for water oxidation. It is found that the NiPS electrocatalyst exhibits good OER performance in 1.0 M KOH solution, i.e., achieving a current density of 20 mA cm-2 at an overpotential of 400 mV and a Tafel slope of 126 mV dec-1, comparable to commercial benchmark RuO2. The ternary NiPS electrocatalyst for the OER is superior to its binary counterparts, i.e., Ni2P and NiS. Density functional theory (DFT) calculations combined with ex situ XPS were performed to obtain further insights into the intrinsic catalytic mechanism of NiPS, and their results clearly revealed that the instability of the NiO intermediate during the OH* → O* process and the easy oxidation of the (PS)3- anion favoring the formation of hydroxyl-based species (i.e., Ni(OH)2/NiOOH) on the surface of the catalyst, which plays a crucial role in facilitating the OER activity. Furthermore, we creatively extended this method to the fabrication of heteroatom substituted catalysts and a new quaternary CoNiP2S2 compound was successfully synthesized for the first time in the same way. The structural properties and electrocatalytic performance towards the OER for CoNiP2S2 (e.g., 20 mA cm-2 at 376 mV) are also systematically investigated in this work.