Grade-targeted nanoparticles for improved hypoxic tumor microenvironment and enhanced photodynamic cancer therapy

Background: The hypoxia of the tumor microenvironment (TME), low transfer efficiency of photosensitizers and limited diffusion distance of reactive oxygen species restrict the application of photodynamic therapy (PDT). Aim: To produce TME-responsive and effective nanoparticles for sensitizing PDT. Materials & methods: CD44 and mitochondria grade-targeted hyaluronic acid (HA)-triphenylphosphine (TPP)-aminolevulinic acid (ALA)-catalase (CAT) nanoparticles (HTACNPs) were synthesized via a modified double-emulsion method. In vitro and in vivo experiments were performed to investigate the antitumor efficacy of HTACNP-mediated PDT. Results: HTACNPs specifically targeted MV3 cells and the mitochondria and produced O₂ to relieve TME hypoxia. HTACNP-mediated PDT produced reactive oxygen species to induce irreversible cell apoptosis. HTACNP-PDT inhibited melanoma growth effectively in vivo. Conclusion: HTACNP-mediated PDT improved TME hypoxia and effectively enhanced PDT for cancer.