Immunogenic Cell Death Induction and Oxygenation by Multifunctional Hollow Silica/Copper-Doped Carbon Dots

Abstract

The metastasis and recurrence of cancer are related to immunosuppression and hypoxia in the tumor microenvironment. Activating immune activity and improving the hypoxic environment face essential challenges. This paper reports on a multifunctional nanomaterial, HSCCMBC, that induces immunogenic cell death through powerful photodynamic therapy/chemodynamic therapy synergistic antitumor effects. The tumor microenvironment changed from the immunosuppressive type to immune type, activated the immune activity of the system, decomposed hydrogen peroxide to generate oxygen based on Fenton-like reaction, and effectively increased the level of intracellular O 2 with the assistance of 3-bromopyruvate, a cell respiratory inhibitor. The structure and composition of HSCCMBC were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, infrared spectroscopy, etc. Oxygen probe RDPP was used to investigate the oxygen level inside and outside the cell, and hydroxyl radical probe tetramethylbenzidine was used to investigate the Fenton-like reaction ability. The immunofluorescence method investigated the expression of various immune markers and hypoxia-inducing factors in vitro and in vivo after treatment. In vitro and in vivo experiments indicate that HSCCMBC is an excellent antitumor agent and is expected to be a candidate drug for antitumor immunotherapy.

Engineering Magnetic Extracellular Vesicles Mimetics for Enhanced Targeting Chemodynamic Therapy to Overcome Ovary Cancer

“…Chemodynamic therapy (CDT), utilizing Fenton agents to converse H 2 O 2 into lethal hydroxyl radicals ( • OH) in situ, has attracted attention as an emerging strategy for cancer therapy . It demonstrates high therapeutic specificity due to the specific overexpression of H 2 O 2 in the tumor microenvironment (TME), leading to localized catalysis with minimal toxicity to normal tissues. , Numerous agents, such as metal ion-containing nanoparticles, organic frameworks, and single-atom nanozymes have been shown to exhibit Fenton or Fenton-like activity to enhance CDT effect. , Iron oxide nanoparticles (Fe 3 O 4 NPs, IONPs) exhibit minor cytotoxicity in normal tissues, while in acidic pH conditions in the tumor region, they can ionize to produce Fe 2+ , catalyzing H 2 O 2 to generate • OH. , Despite the high levels in cancer cells (0.1–1 mM), the intratumoral H 2 O 2 remains insufficient for IONPs to produce adequate • OH for desired CDT efficacy. , Additionally, overproduced intracellular GSH mediates potent • OH scavenging in cancer cells, thereby weakening the effect. , Consequently, the simultaneous amplification of the intracellular H 2 O 2 supply for Fenton reactions and GSH elimination in a single formulation is highly desirable.…”