Molecular engineering to construct specific cancer cell lysosome targeting photosensitizer by adjusting the proton binding ability

Minimizing the concomitant damage to healthy tissues is the key factor to guarantee precise and efficient photodynamic therapy (PDT). Herein, a specifically cancer cell lysosome targeted pre-photosensitizer with the suitable pH-response range (pH < 5.0) has been rationally designed by simple molecular engineering and successfully applied for switch-on PDT, which is further confirmed by the single crystal structure, pH test, cell uptake, and in vivo treatments. Fluorescence imaging on mouse model evidences that it is “off” in normal tissue and “on” in tumor region. This lysosome-targeting activated pre-photosensitizer provides new opportunities in the rational design of tumor specifically responsive photosensitizer.