Metal-organic framework combined with CaO₂ nanoparticles for enhanced and targeted photodynamic therapy

Photodynamic therapy (PDT) has been rapidly developed as an effective therapeutic approach in clinical settings. However, hypoxia seriously limits the effectiveness of PDT. Here, we report a porphyrin-based metal-organic framework combined with hyaluronate-modified CaO₂ nanoparticles (PCN-224-CaO₂-HA) to target and enhance PDT efficacy. CaO₂ reacts with H₂O or weak acid to produce O₂, overcoming the hypoxia problem. Hyaluronate protects CaO₂ and specifically targets the CD44 receptor, which is highly expressed on tumor cell membranes, performing targeted therapy. After PDT treatment in vitro, the survival rates of 4T1 and MCF-7 tumor cells were 14.58% and 22.45%, respectively. The fluorescence imaging showed that PCN-224-CaO₂-HA effectively aggregated in the tumor after 12 h of its intravenous injection into tumor-bearing mice. PCN-224-CaO₂-HA exhibited efficacious tumor growth inhibition via enhanced PDT. Overall, this nanosystem providing in situ oxygen production was successfully used for targeted PDT with a significantly enhanced therapeutic efficacy in vitro and in vivo.