ATP-Activatable Photosensitizer Enables Dual Fluorescence Imaging and Targeted Photodynamic Therapy of Tumor.

Targeted delivery of intracellular stimuli-activatable photosensitizers (PSs) into tumor cells to achieve selective imaging and on-demand photodynamic therapy (PDT) of tumors has provided a vital opportunity for precise cancer diagnosis and therapy. In this paper, we report a tumor targeting and adenosine triphosphate (ATP)-activatable nanophotosensitizer Apt-HyNP/BHQ2 by modifying hybrid micellar nanoparticles with both nucleolin-targeting aptamer AS1411 and quencher BHQ2-labeled ATP-binding aptamer BHQ2-ATP-apt. We demonstrated that both of the fluorescence emissions at 555 and 627 nm were quenched by BHQ2 in Apt-HyNP/BHQ2, resulting in low PDT capacity. After selective entry into tumor cells through nucleolin-mediated endocytosis, the high concentration of intracellular ATP could bind to BHQ2-ATP-apt and trigger Apt-HyNP/BHQ2 dissociation, leading to turning "on" both fluorescence and PDT. The "off-on" fluorescence emissions at both 555 and 627 nm were successfully applied for dual color fluorescence imaging of endogenous ATP levels and real-time monitoring of intracellular activation of Apt-HyNP/BHQ2 in tumor cells. Moreover, imaging-guided precise PDT of tumors in living mice was also demonstrated, allowing for selective ablation of tumors without obvious side effects. This study highlights the potential of using a combination of tumor-targeting and ATP-binding aptamers to design ATP-activatable PSs for both fluorescence imaging and imaging-guided PDT of tumors in vivo.