Enzyme and pH dual-responsive hyaluronic acid nanoparticles mediated combination of photodynamic therapy and chemotherapy

Hyaluronic acid (HA) is a natural biopolymer that can target to tumor cells due to CD44 receptors overexpressed in tumor cells. Here, a theranostic nanoparticle HA-Ce6 (DOX) with enzyme and pH dual-responsive is presented, which combined HA and a highly promised photosensitizer chlorin e6 (Ce6) using adipic dihydrazide (ADH) as a linker. The hydrazide group on its surface can efficiently conjugate doxorubicin to form HA-Ce6 (DOX) nanoparticles through the pH-sensitive hydrazone bond. In this study, the dual-response of HA-Ce6 (DOX) nanoparticles in the tumor cell are discussed. The HA-Ce6 (DOX) nanoparticles showed an average size of 90 nm with a uniform spherical morphology. In vitro drug release studies showed that HA-Ce6 (DOX) accomplished rapid drug release under acid conditions and enzyme stimulating. Confocal images revealed that the nanoparticles enhance the cellular accumulation of DOX and Ce6 in A549 cells. The therapeutic efficacy of HA-Ce6 (DOX) nanoparticles in A549 cells in vitro was evaluated through the MTT assay. The results showed that the therapeutic efficacy of HA-Ce6 (DOX) nanoparticles against A549 cells was remarkably enhanced compared with free DOX and free Ce6. These results indicate that the HA-Ce6 (DOX) nanoparticles could be a promising delivery system for photodynamic therapy and chemotherapy.