Metal-Phenolic Nanomaterial with Organelle-Level Precision Primes Antitumor Immunity via mtDNA-dependent cGAS-STING Activation.

New generation of nanomaterials with organelle-level precision provide significant promise for targeted attacks on mitochondria, exhibiting remarkable therapeutic potency. Here, we report a novel amphiphilic phenolic polymer (PF) for the mitochondria-targeted photodynamic therapy (PDT), which can trigger excessive mitochondrial DNA (mtDNA) damage by the synergistic action of oxidative stress and furan-mediated DNA cross-linking. Moreover, the phenolic units on PF enable further self-assembly with Mn2+ via metal-phenolic coordination to form metal-phenolic nanomaterial (PFM). We focus on the synergistic activation of the cGAS-STING pathway by Mn2+ and tumor-derived mtDNA in tumor-associated macrophages (TAMs), and subsequently repolarizing M2-like TAMs to M1 phenotype. We highlight that PFM facilitates the cGAS-STING-dependent immunity at the organelle level for potent antitumor efficacy.

Phase measuring deflectometry for convex aspheric surface measurement.

This paper introduces what we believe to be a novel approach to accurately measure the shape of convex aspherical surfaces with large slope gradients. This approach employs a pre-distortion system to enhance the visibility of the structured light pattern that is captured by camera. The data processing involves iterative methods to obtain surface shape data. The initial step in the experimental calibration involves establishing a reference plane, which serves as the starting point for the iterative process. The calculation for slope is subsequently utilized to determine the initial slope of the surface under test, and the height of the tested element is derived by integrating these slopes. Through multiple iterations and continuous updating of the surface height, the precise and authentic true surface height is ultimately achieved. The method's accuracy is assessed through the measurement of a highly steep convex aspherical area with a diameter of 5.2 mm and a radius of curvature of approximately 7.7 mm. The proposed method demonstrates root mean square accuracy that can reach half a wavelength when compared to the measurement results obtained from high-precision profilers.

Acid-Responsive Micelles Releasing Cinnamaldehyde Enhance RSL3-Induced Ferroptosis in Tumor Cells.

Ferroptosis is a novel type of regulated cell death characterized by the accumulation of lipid peroxides to lethal levels. Most tumor cells are extremely vulnerable to ferroptosis due to the high levels of reactive oxygen species (ROS) produced by their active metabolism. Therefore, tumor cells rely on glutathione (GSH) to reduce lipid peroxides catalyzed by glutathione peroxidase 4 (GPX4), and this pathway is also an important target for a variety of drugs that promote tumor cell ferroptosis. Herein, RSL3@PCA was designed to simultaneously deplete intracellular GSH and inhibit the activity of GPX4, thereby significantly promoting tumor cell ferroptosis. RSL3@PCA was successfully prepared by encapsulating a selective inhibitor of GPX4 into acid-responsive nanoparticle PCA. After being taken up by tumor cells, the acid-responsive nanoparticle gradually degraded to release cinnamaldehyde (CA) and the encapsulated RSL3. CA and RSL3 block the reduction of lipid peroxides in cells, thereby inducing ferroptosis. By a cytotoxicity assay and 4T1 cell xenotransplantation model, we confirmed that RSL3@PCA has excellent inhibition of tumor growth without significant toxicity to normal cells and tissues and still has a good therapeutic effect on tumor cells that are resistant to conventional chemotherapy drugs. This work provides new drug combinations for promoting ferroptosis in tumor cells without severe side effects in normal organs.

A glutathione-responsive polyphenol - Constructed nanodevice for double roles in apoptosis and ferroptosis.

Combination chemotherapy regimens have been put forward to achieve a synergistic effect and reduce drug doses for the clinical applications of cancer treatment. One of the principal approaches for killing cancer cells involves triggering apoptotic cell death with anti-cancer drugs. Nevertheless, the efficacy of apoptosis induction in tumors is often restricted on account of intrinsic or acquired resistance of cancer cells to apoptosis. Ferroptosis, which involves reactive oxygen species (ROS), is another way to regulate cell death. Doxorubicin (DOX), a commonly used chemotherapeutic agent, can enter the nucleus and destroy tumor cells while also affecting mitochondria by producing semiquinone radicals. Therefore, a drug system combining ferroptosis and apoptosis, bridged by DOX-induced ROS, was proposed to be designed. Herein, we employed a facile and effective self-assembly method to prepare DOX-loaded nanocomplexes by DOX, Pluronic F-68, tannic acid (TA), and iron ions. TA and iron ions could not only improve the stability of nanocarrier but also facilitate achieving a ferroptotic effect. As a result, DOX@F-68/TA/Fe3+ nanocomplexes showed a strong pro-apoptotic effect as well as an increase in intracellular oxidative stress. The improved oxidative stress further resulted in the ferroptosis of tumor cells. In vivo experiments demonstrated that DOX@F-68/TA/Fe3+ efficiently targeted the tumor following intravenous injection and successfully inhibited tumor development.