Oxygen self-sufficient NIR-activatable liposomes for tumor hypoxia regulation and photodynamic therapy

The inherent hypoxic environment in tumors severely resists the efficacy of photodynamic therapy. To address this problem, herein, the strategy of using oxygen self-sufficient liposomes (denoted as CaO₂/B1/NH₄HCO₃ lipo), which contained aza-BODIPY dye (B1) and CaO₂ nanoparticles in the hydrophobic layer and NH₄HCO₃ in the hydrophilic cavity, was presented to overcome hypoxia-associated photodynamic resistance. Under near-infrared (NIR) irradiation, NIR-absorbable B1 was activated to induce hyperthermia and further triggered the decomposition of NH₄HCO₃. Subsequently, with the aid of NH₄HCO₃ and CaO₂ nanoparticles, oxygen was rapidly and self-sufficiently generated, during which clean by-products were produced. Furthermore, the increased amount of oxygen promoted the singlet oxygen production in the presence of B1, which served as a photosensitizer because of the heavy atom effect. The oxygen self-sufficient system improved the anticancer efficiency and alleviated the hypoxic environment in vivo, which demonstrated a valuable attempt to regulate intratumoral hypoxia and overcome the limitation of current photodynamic therapy systems. To our knowledge, this highlights the first example of using NIR light to activate CaO₂ nanoparticle-containing liposomes for the modulation of the hypoxic environment in tumors.