Synergistic Sono-Gene Therapy of Gastric Cancer via Nanoparticle-Based Delivery of Chlorin e6 and siRNA

Gastric cancer remains one of the most pressing global health challenges, with its high mortality rate primarily attributed to aggressive tumor invasiveness and strong metastatic potential. This grim scenario underscores the urgent need for effective, feasible, and innovative therapeutic strategies. In this study, we developed a targeted nanoparticle system (iBCsi) that codelivers the sonosensitizer chlorin e6 (Ce6) and small interfering RNA (siRNA) for sono-gene therapy. It has a size of 100.21 ± 1.22 nm. This system enables the implementation of a “suppress EMT-promote apoptosis” strategy: Specifically, the siRNA reduces tumor invasiveness via downregulating LINC00963, an overexpressed long noncoding RNA (LncRNA) known to drive epithelial–mesenchymal transition (EMT). Concurrently, upon ultrasound irradiation, iBCsi generates high levels of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis. This synergistic therapeutic approach successfully suppresses tumor growth and EMT via the combination of gene silencing and sonodynamic therapy, not only deepening the mechanistic understanding of gastric cancer therapy but also enhancing its translational potential within precision oncology.