Pyroptosis Induction with Nanosonosensitizer‐Augmented Sonodynamic Therapy Combined with PD‐L1 Blockade Boosts Efficacy against Liver Cancer

Abstract

Induction of pyroptosis can promote anti‐PD‐L1 therapeutic efficacy due to the release of pro‐inflammatory cytokines, but current approaches can cause off target toxicity. Herein, a phthalocyanine‐conjugated mesoporous silicate nanoparticle (PMSN) is designed for amplifying sonodynamic therapy (SDT) to augment oxidative stress and induce robust pyroptosis in tumors. The sub‐10 nm diameter structure and c(RGDyC)‐PEGylated modification enhance tumor targeting and renal clearance. The unique porous architecture of PMSN doubles ROS yield and enhances pyroptotic cell populations in tumors (25.0%) via a cavitation effect. PMSN‐mediated SDT treatment efficiently reduces tumor mass and suppressed residual tumors in treated and distant sites by synergizing with PD‐L1 blockade (85.93% and 77.09%, respectively). Furthermore, loading the chemotherapeutic, doxorubicin, into PMSN intensifies SDT‐pyroptotic effects and increased efficacy. This is the first report of the use of SDT regimens to induce pyroptosis in liver cancer. This noninvasive and effective strategy has potential for clinical translation.

Microenvironment-responsive metal-phenolic network release platform with ROS scavenging, anti-pyroptosis, and ECM regeneration for intervertebral disc degeneration

“…The accumulation of ROS and mitochondrial toxicity can mediate cellular pyroptosis through multiple pathways, such as the ROS-mediated promotion of the inflammatory vesicle NLRP3/caspase-1/GSDMD signaling pathway [ [51] , [52] , [53] ]. Given the close relationship between ROS and cellular pyroptosis, we hypothesized that TMP@Alg-PBA/PVA may also inhibit pyroptosis.…”

A Cascade-Amplified Pyroptosis Inducer: Optimizing Oxidative Stress Microenvironment by Self-Supplying Reactive Nitrogen Species Enables Potent Cancer Immunotherapy

“…The generation of reactive oxygen species (ROS) is a well-known mechanism associated with the initiation of pyroptosis. , Various ROS-based pyroptosis therapies, including photodynamic therapy (PDT), − sonodynamic therapy (SDT), , chemodynamic therapy (CDT) (Fenton and Fenton-like nanocatalysis drugs), , chemotherapy (CT), and ion interference therapy, , are subsequently reported. As a biological messenger molecule, nitric oxide (NO) plays an important role in the physiology and pathophysiology system.…”