Ultrasound-responsive PLGA nanoparticles co-loaded with celecoxib and catalase enhance the therapeutic efficacy of imatinib in gastrointestinal stromal tumors.

Abstract

The therapeutic efficacy of imatinib (IM) in gastrointestinal stromal tumors (GISTs) is often limited by inadequate intratumoral drug accumulation and an abnormal tumor microenvironment. In this study, an ultrasound-responsive poly(lactic-co-glycolic acid) (PLGA) nanoparticle system, designated CXB/CAT@PFP-PLGA NPs, was developed for the co-delivery of celecoxib (CXB) and catalase (CAT) to enhance the antitumor efficacy of IM. The nanoparticles were characterized in terms of their physicochemical properties, ultrasound responsiveness, and oxygen-generating capability. Their ability to potentiate IM therapy was evaluated both in vitro and in vivo, while biodistribution and biosafety were assessed in vivo. The results showed that CXB/CAT@PFP-PLGA NPs exhibited a relatively uniform size distribution and successfully co-encapsulated CXB and CAT. Upon ultrasound irradiation, the nanoparticles underwent phase transition, thereby triggering drug release. In vitro, CXB/CAT@PFP-PLGA NPs enhanced the inhibitory effect of IM by reducing cell viability, promoting apoptosis, and inhibiting cell migration. In vivo, the nanosystem improved the antitumor efficacy of IM, accumulated at the tumor site, suppressed tumor growth, and showed no evident systemic toxicity. Collectively, these findings suggest that CXB/CAT@PFP-PLGA NPs may represent a promising strategy for enhancing IM therapy in GIST.