Folic acid-targeted PLGA nanoparticles co-delivering doxorubicin and MnTPP enable ultrasound-triggered synergy and apoptosis in nasopharyngeal carcinoma.

Although the co-delivery of chemotherapeutic agents and sonosensitizers has been studied for years, developing efficient co-delivery nanocarriers that combine chemotherapy and sonodynamic therapy (SDT) with precise targeting remains a challenge. In this study, we prepared folic acid (FA)-functionalized poly(lactic-co-glycolic acid) (PLGA) nanoparticles (FPMD NPs) co-loaded with doxorubicin (Dox) and the sonosensitizer manganese(III) meso-tetrakis(4-carboxyphenyl)porphyrin (MnTPP) via a double-emulsion solvent evaporation method. Upon ultrasound irradiation, oxidative stress and apoptotic signaling were activated, which was revealed by transcriptomic analysis. In vivo, the combination of FPMD NPs with ultrasound achieved tumor targeting and tumor growth suppression in BALB/c nude mice bearing HNE-1 xenografts. The body weight of BALB/c nude mice remained stable and no histopathological abnormalities in major organs were detected. Overall, the FPMD NPs successfully integrate MnTPP-mediated SDT with Dox chemotherapy and demonstrate strong antitumor efficacy and favorable biosafety, highlighting their potential for synergistic SDT and chemotherapy in nasopharyngeal carcinoma treatment.