Nanotransferrin-Based Programmable Catalysis Mediates Three-Pronged Induction of Oxidative Stress to Enhance Cancer Immunotherapy

Abstract

Current oxidative stress amplifying strategies for immunogenic cell death (ICD) promotion are mainly restricted to immune tolerance induced by adaptive cellular antioxidation, limited tumor-selectivity, and tumoral immunosuppression. Herein, a facile and efficient scenario of genetically engineering transferrin-expressing cell membrane nanovesicle encapsulated IR820-dihydroartemisinin nanomedicine (Tf@IR820-DHA) was developed to boost a-PD-L1mediated immune checkpoint blocking (ICB) via synergetic triple stimuli-activated oxidative stress-associated ICD. We demonstrate that the engineered transferrin of Tf@IR820-DHA has excellent tumor targeting and Fe(III)-loading properties and thus delivered Fe(III) and IR820-DHA nanoparticles (NPs) to the lesion location effectively. We found that the self-carrying Fe(III)-mediated programmable catalysis of DHA and glutathione (GSH) depletion generated plenty of reactive oxygen species (ROS). Moreover, DHA also acted as an immunomodulator to decrease the number of T regulatory cells, thereby remodeling the tumor immune microenvironment and achieving double T cell activation. Furthermore, the IR820 molecule served as a competent sonosensitizer to produce ROS under ultrasound activation and guide precise immunotherapy via fluorescent/photoacoustic (FL/PA) imaging. Through its three-pronged delivery of stimuli-activated oxidative stress (DHA-induced chemodynamic therapy, catalysis-conferred GSH depletion, and IR820-mediated sonodynamic therapy), Tf@ IR820-DHA caused high levels of targeted ICD. This significantly increased the proportions of IFN-γ-secreting T cells (CD4 + T and CD8 + T) and enhanced a-PD-L1-mediated ICB against primary and distant tumors, which represents a promising approach for cancer nanoimmunotherapy.

Connecting Calcium-Based Nanomaterials and Cancer: From Diagnosis to Therapy

“…In recent years, studies based on biodegradable nanomaterials have shown that the inherent anti-cancer activity can be regulated by disturbing the intracellular ion balance due to the related biological activity of their degradation products, which is known as ion interference therapy (IIT) [ 110 , 111 ]. Of these aspects, iron-based materials (“ferroptosis”) [ 112 – 114 ] and sodium chloride [ 115 , 116 ] provided the good demonstration. Therefore, ion-interfering cancer therapy is expected to become a new therapeutic tool as a supplement to traditional clinical cancer therapy.…”

Identification of Ferroptosis-Associated Long Noncoding RNA Prognostic Model and Tumor Immune Microenvironment in Thyroid Cancer

“…Bergdorf et al demonstrated that dendritic cells and neutrophils could promote lymph node (LN) metastasis and affect prognosis through the LAG3-mediated immunosuppression in PTCs [ 11 ]. The latest ICB synergetic triple stimuli-activated nanoimmunotherapy has represented that more potential immune regimens effectively improved the overall response of cancer patients [ 12 ]. In summary, ferroptosis-associated lncRNAs have significant potential to become prognostic assessment markers and provide immunotherapeutic strategies for TC.…”

Inhibition mechanism of melanin formation based on antioxidant scavenging of reactive oxygen species

“…Healthy embryos of 72 hpf (melanin formation) were randomly selected under a continuous magnification microscope using the plastic dropper. 38,39 A 6-well cell culture plate was used as the experimental carrier, and 30 embryos were added into each well. After the culture water was dried with a plastic pipette, 5.0 mL of the diluent prepared from the test sample was added to each well (5 concentrations) of the 6-well cell culture plate above.…”