Engineered hollow mesoporous organosilica nanoparticles with pH/GSH dual-responsiveness for synergistic photothermal-chemotherapy

Nanomedicines can overcome several limitations of traditional chemotherapeutics such as imprecise targeting and severe side effects. However, challenges remain in selective delivery, targeted accumulation, and spatiotemporal control of release. This study aims to develop a pH- and glutathione (GSH)-responsive nanodrug delivery system that integrates photothermal therapy (PTT) and chemotherapy. We designed and synthesized degradable hollow mesoporous organosilica nanoparticles (DHMONs) with tetrasulfide bonds, which were self-assembled with copper sulfide nanoparticles (CuS NPs) via surface modification. These DHMONs@CuS nanoparticles utilize the hollow structure for a large surface area and high drug-loading capacity, enabling the encapsulation of the chemotherapeutic drug doxorubicin (DOX) for synergistic photothermal-chemotherapeutic treatment. Additionally, the surface modification of these nanoparticles with hyaluronic acid (HA) facilitates active targeting of tumor cells overexpressing CD44 receptors. The system exhibits dual responsiveness to pH and GSH, aiding precise drug release within the tumor microenvironment. Following studies demonstrate that this nanosystem effectively inhibits tumor growth, showing promising prospects for application in multimodal cancer treatment.