ROS-responsive Nanoparticles for Synergistic Sonodynamic and Calcium Dysregulation Therapy of Endometrial Cancer

ABSTRACT: Non-surgical treatment for endometrial cancer is limited by poor tumor targeting and the immunosuppressive microenvironment of conventional progesterone-based therapies. Emerging evidence highlights the therapeutic potential of targeting calcium homeostasis, while advances in nanomedicine enable the integration of sonodynamic therapy with molecular targeted drug delivery. Herein, we designed an ultrasound-responsive nanoparticles (MP-RSP/Ce6/MDP) that co-loads the sonosensitizer chlorin e6 (Ce6) and the calcium channel blocker manidipine (MDP), enabling synergistic combination of sonodynamic therapy and calcium homeostasis modulation for precision non-surgical treatment of endometrial cancer. This platform features a ROS-responsive polymer shell. Upon ultrasound activation, Ce6 generates cytotoxic reactive oxygen species, which cleave the shell and trigger the release of MDP. The combination of ROS generation and calcium influx inhibition synergistically induces severe endoplasmic reticulum stress, leading to immunogenic cell death and subsequent reprogramming of the tumor immune microenvironment. This sonodynamic therapy approach further synergizes with anti-PD-1 antibodies, resulting in enhanced therapeutic outcomes in vivo. In addition, MP-RSP-based nanoparticles efficiently accumulated in tumors, as confirmed by SPECT/CT imaging using co-assembled MP-RSP/99mTc-RSP nanoparticles. By integrating tumor targeting, ultrasound responsiveness, and immunomodulatory functions, this nanoparticle offers a novel strategy for the treatment of endometrial cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE325161 | GEO | 2026/10/07

REPOSITORIES: GEO