Rationally Integrated Precise ER-targeted And Oxygen-compensated Photodynamic Immunostimulant for Immunogenicity-boosted Tumor Therapy.
Yanrong QianMan WangYulin XieQianqian SunMinghong GaoChunxia LiPublished in: Advanced healthcare materials (2023)
Notwithstanding that immunotherapy has made eminent clinical breakthroughs, activating the immunogenicity and breaking the immunosuppressive tumor microenvironment (ITME) remains tempting yet challenging. Herein, a customized-designed immunostimulant was engineered for attenuating ITME and eliciting an immune response to address this challenge head-on. This immunostimulant was equipped with dual silica layers coated upconversion nanoparticles (UCNPs) as nanocarriers modified with N-p-Tosylglycine, in which the dense silica for chlorin e6 (Ce6) and the glutathione (GSH)-responsive degradable silica for loading resveratrol (RES) (UCNPs@SiO 2 -Ce6@MON(RES)@ER (UCSMR ER )). On the one hand, UCSMR ER was positioned accurately in the endoplasmic reticulum (ER) guided by the ER-targeted molecular N-p-Tosylglycine. This precise ER-targeted photodynamic therapy (PDT) could generate reactive oxygen species (ROS) in situ under the 980 nm laser irradiation, which not only induced severe cell death directly but also caused intense ER stress-based immunogenic cell death (ICD) effects, triggering a tumor immune response. On the other hand, tumor hypoxia aggravated by the PDT process was effectively alleviated by RES released on-demand, which reduced oxygen consumption by impairing the mitochondrial electron transport chain (ETC). This integrated precise ER-targeted and oxygen-compensated strategy maximized the PDT effect and potentiated ICD-associated immunotherapy, which availed to attenuate ITME, activate tumor immunogenicity and further magnify anti-tumor effect. This innovative concept about PDT and immunotherapy sheds light on the cancer-related clinical application. This article is protected by copyright. All rights reserved.
Keyphrases
- endoplasmic reticulum
- photodynamic therapy
- cell death
- cancer therapy
- estrogen receptor
- breast cancer cells
- fluorescence imaging
- reactive oxygen species
- immune response
- drug delivery
- dna damage
- oxidative stress
- stem cells
- radiation therapy
- endothelial cells
- cell proliferation
- toll like receptor
- mesenchymal stem cells
- early onset
- cell cycle arrest
- radiation induced
- drug induced
- light emitting