Photo-generating Type-I ROS and aryl radicals by mitochondrial-targeting oxime-ester photogenerator for pyroptosis-mediated anti-hypoxia photoimmunotherapy.

Pyroptosis is an inflammatory form of programmed cell death with great potential in cancer immunotherapies. Photodynamic therapy (PDT) represents a promising treatment modality to trigger pyroptosis. However, the hypoxic microenvironment inside the tumors often induces limited therapeutic efficacy.

Cell-membrane targeting sonodynamic therapy combination with FSP1 inhibition for ferroptosis-boosted immunotherapy.

Cell membrane targeting sonodynamic therapy could induce the accumulation of lipid peroxidation (LPO), drive ferroptosis, and further enhances immunogenic cell death (ICD) effects. However, ferroptosis is restrained by the ferroptosis suppressor protein 1 (FSP1) at the plasma membrane, which can catalyze the regeneration of ubiquinone (CoQ10) by using NAD(P)H to suppress the LPO accumulation. This work describes the construction of US-active nanoparticles (TiF NPs), which combinate cell-membrane targeting sonosensitizer TBT-CQi with FSP1 inhibitor (iFSP1), facilitating cell-membrane targeting sonodynamic-triggered ferroptosis.

Mitochondria-Targeting Type-I Photodynamic Therapy Based on Phenothiazine for Realizing Enhanced Immunogenic Cancer Cell Death via Mitochondrial Oxidative Stress.

Purpose: Photo-immunotherapy faces challenges from poor immunogenicity and low response rate due to hypoxic microenvironment. This study presents Rh-PTZ, a small organic molecule with a D-π-A structure, that simultaneously amplifies mitochondria-targeted type-I PDT-dependent immune stimulation for the treatment of hypoxic cancer.

Methods: The hydrophobic Rh-PTZ was encapsulated into F127 to prepare Rh-PTZ nanoparticles (Rh-PTZ NPs).

Nucleus-Targeted Sonosensitizer Activates the cGAS-STING Pathway for Tumor Sonodynamic Immunotherapy.

A nucleus is crucial for both sonodynamic therapy (SDT) and antitumor immunity. However, how to burst ROS generation , accurately damage a nucleus, and meanwhile activate a cGAS-STING pathway-induced innate immune response are still a great challenge. Here, we present TBzT-CPi, a small molecule with a D-A-π-A1 structure that simultaneously amplifies nucleus-targeted SDT and cGAS-STING pathway-dependent immune stimulation.

NIR-II Emissive Superoxide Radical Photogenerator for Photothermal/Photodynamic Therapy against Hypoxic Tumor.

Due to the "Achilles' heels" of hypoxia, complicated location in solid tumor, small molecular photosensitizers with second near-infrared window (NIR-II) fluorescence, type-I photodynamic therapy (PDT), and photothermal therapy (PTT) have attracted great attention. However, these photosensitizers are still few but yet challenging. Herein, an "all in one" NIR-II acceptor-donor-acceptor fused-ring photosensitizer, Y6-Th, is presented for the in-depth diagnosis and efficient treatment of cancer.