Improved cancer phototheranostic efficacy of hydrophobic IR780 via parenteral route by association with tetrahedral nanostructured DNA

As a photosensitizer with effective photothermal (PTT) and photodynamic (PDT) response, IR780 has been widely explored as promising cancer phototheranostic molecule. However, the systematic administration of IR780 usually suffers from poor water solubility and low photostability, so that it cannot be administrated by parenteral route. In this study, we design a tetrahedral DNA (Td)-based nanosystem to load IR780 ([email protected]) via electrostatic interaction and π-π stacking. After encapsulation, the water solubility and photostability of IR780 have been greatly improved, and the [email protected] shows an appropriate nanoformulated size (224 nm) to facilitate hyperthermia-mediated tumor targeting by EPR effect. The nanostructure of Td is proved to be crucial for the proper size and good stability of [email protected] nanoformulation for in vivo application. The in vitro and ex vivo PTT/PDT efficiencies of IR780 are improved in [email protected] group. In the tumor-bearing mice, the accumulation of IR780 in tumor site is significantly high in [email protected] group. Under near-infrared laser irradiation, the intravenous administration of [email protected] promotes the tumor imaging and enhances anti-tumor effect than IR780 treatment. In summary, the proposed strategy shows promising effect in facilitating intravenous injection of IR780 and enhancing the phototheranostic efficacy for cancer treatment.