Pyroptosis activation by photodynamic-boosted nanocatalytic medicine favors malignancy recession

Oxidative Medicine and Cellular Longevity

et al. 2022

Objective. The off-target effects and severe side effects of PPARα and LXRα agonists greatly limit their application in atherosclerosis (AS). Therefore, this study intended to use mesoporous silica nanoparticles as carriers to generate MnO nanoparticles in situ with T1WI-MRI in mesoporous pores and simultaneously load PPARα and LXRα agonists. Afterward, cRGD-chelated platelet membranes can be used for coating to construct a new nanotheranostic agent. Methods. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were synthesized by a chemical method. Dynamic light scattering (DLS) was utilized to detect the size distribution and polydispersity index (PDI) of the nanoparticles. The safety of the nanoparticles was detected by CCK8 in vitro and HE staining and kidney function in vivo. Cell apoptosis was detected by flow cytometry detection and TUNEL staining. Oxidative stress responses (ROS, SOD, MDA, and NOX levels) were tested via a DCFH-DA assay and commercial kits. Immunofluorescence and phagocytosis experiments were used to detect the targeting of nanoparticles. Magnetic resonance imaging (MRI) was used to detect the imaging performance of cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles. Using western blotting, the expression changes in LXRα and ABCA1 were identified. Results. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were successfully established, with a particle size of approximately 150 nm and PDI less than 0.3, and showed high safety both in vitro and in vivo. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed good targeting properties and better MRI imaging performance in AS. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed better antioxidative capacities, MRI imaging performance, and diagnostic and therapeutic effects on AS by regulating the expression of LXRα and ABCA1. Conclusion. In the present study, cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles with high safety and the capacity to target vulnerable plaques of AS were successfully established. They showed better performance on MRI images and treatment effects on AS by promoting cholesterol efflux through the regulation of ABCA1. These findings might address the problems of off-target effects and side effects of nanoparticle-mediated drug delivery, which will enhance the efficiency of AS treatment and provide new ideas for the clinical treatment of AS.

Section: Discussionmentioning

confidence: 99%

Targeted Diagnosis, Therapeutic Monitoring, and Assessment of Atherosclerosis Based on Mesoporous Silica Nanoparticles Coated with cRGD-Platelets

Oxidative Medicine and Cellular Longevity

et al. 2022

“…(2) Compared with natural enzymes and organocatalysts, the catalytic activity or efficiency of nanozymes still remains at a relatively low level at present. 134 From this perspective, measures to tune sizes and modify surfaces should be taken to achieve greater efficiency. For instance, the molecularly imprinted polymers can be employed to encapsulate the nanozyme to significantly improve its catalytic selectivity; 135 or nanozymes and natural enzymes could be combined simultaneously to achieve specific recognition and catalysis of target molecules.…”

Section: Discussionmentioning

confidence: 99%

Breakthroughs in nanozyme-inspired application diversity

Song

2023

Mater. Chem. Front.

Self Cite

“…Recogniz- ing this, Chen and collaborators successfully developed a nanocatalytic construct, MMSN-cRGD@Ce6 (Figure 9b), that was found to induce synergistic photochemical effects and trigger pyroptosis. 111 MMSN-cRGD@Ce6 consists of magnetic mesoporous silica nanoparticle (MMSN) vehicles containing Fe 3 O 4 (to promote the Fenton reaction), Ce6 (included as a photosensitizer), and an RGD peptide sequence (to assist in tumor targeting). MMSN-cRGD@Ce6 was able to overcome hypoxia-induced resistance, both in vitro and in vivo.…”

Section: Photoredox Catalysis In Cellsmentioning

confidence: 99%

Photon-Controlled Pyroptosis Activation (PhotoPyro): An Emerging Trigger for Antitumor Immune Response

Kim

Rha

et al. 2023

J. Am. Chem. Soc.

Pyroptosis refers to the process of gasdermin-mediated lytic programmed cell death (PCD) characterized by the release of pro-inflammatory cytokines. Our knowledge of pyroptosis has expanded beyond the cellular level and now includes extracellular responses. In recent years, pyroptosis has attracted considerable attention due to its potential to induce host immunity. For instance, at the 2022 International Medicinal Chemistry of Natural Active Ligand Metal-Based Drugs (MCNALMD) conference, numerous researchers demonstrated an interest in photon-controlled pyroptosis activation ("PhotoPyro"), an emerging pyroptosis-engineered approach for activating systemic immunity via photoirradiation. Given this enthusiasm, we share in this Perspective our views on this emerging area and expound on how and why "PhotoPyro" could trigger antitumor immunity (i.e., turning so-called "cold" tumors "hot"). In doing so, we have tried to highlight cutting-edge breakthroughs in PhotoPyro while suggesting areas for future contributions. By providing insights into the current state of the art and serving as a resource for individuals interested in working in this area, it is hoped that this Perspective will set the stage for PhotoPyro to evolve into a broadly applicable cancer treatment strategy.