Near-Infrared Light-Triggered Nanobomb For In Situ On-Demand Maximization Of Photothermal/Photodynamic Efficacy For Cancer Therapy

Currently, the in situ on/off switch of PTT/PDT reagents for tumor treatment has evoked considerable interest in the field of cancer therapy. However, the actual PTT/PDT therapy efficacy in tumor treatment is largely restricted by the PTT/PDT reagents' aggregation issues during their release from the hydrophobic carrier to the hydrophilic tumor microenvironment. Thus, it remains a challenge to break through the therapy barrier caused by the PTT/PDT agent aggregation and achieve substantial improvement of anticancer efficacy. In this work, we developed a novel near-infrared (NIR) light-responsive and gas bubble-generated liposomal nanobomb (Cy/Ce6/CO2-Lip-FA) through the co-encapsulation of PTT/PDT reagents with gas precursor into the hydrophobic and hydrophilic regions of liposomes, respectively, in order to overcome the aggregation issues and substantially improve the synergistic PTT/PDT efficacy. Upon arrival at the tumor region, the PS phototoxicity of Cy/Ce6/CO2-Lip-FA could be effectively switched on through CO2 generation induced by the PTT effect of Cypate upon NIR irradiation. The gas bubble burst can remarkably suppress the aggregation of Cypate/Ce6 and extremely enhance the synergistic PTT/PDT efficacy. These results indicate that the proposed NIR-responsive and gas bubble-functionalized liposomal nanobomb is a highly promising platform for tumor treatment with better therapeutic efficacy.