Real-time in vivo pH imaging in the tumor, as well as designing therapies responsive to the acidic tumor microenvironment to achieve optimized therapeutic outcomes have been of great interests in the field of nanomedicine. Herein, a pH-responsive near-infrared (NIR) croconine (Croc) dye is able to induce the self-assembly of human serum albumin (HSA) to form HSA-Croc nanoparticles useful not only for real-time ratiometric photoacoustic pH imaging of the tumor, but also for pH responsive photothermal therapy with unexpected great performance against tumors with relatively large sizes. Such HSA-Croc nanoparticles upon intravenous injection exhibit efficient tumor homing. As the decrease of pH, the absorption of Croc at 810 nm would increase while that at 680 nm would decrease, allowing real-time pH sensing in the tumor by double-wavelength ratiometric photoacoustic imaging, which reveals the largely decreased pH inside the cores of large tumors. Moreover, utilizing HSA-Croc as a pH-responsive photothermal agent, effective photothermal ablation of large tumors is realized, likely owing to the more evenly distributed intratumoral heating compared to that achieved by conventional pH-insensitive photothermal agents, which are effective mostly for tumors with small sizes.
