In Situ Self-Assembled Nanoparticles for Cascade-Instructed Photodynamic Therapy and Real-Time Treatment Feedback Imaging.

Although the cancer treatment efficacy has significantly improved, delayed and isolated evaluation methods are difficult to prevent excessive or insufficient treatment. Therefore, the single molecule for simultaneous therapy and feedback has become a promising tool. Herein, we develop an in situ self-assembled probe (HPO-CYFF-TPP) for cascade-instructed therapy and feedback imaging. Under the dephosphorylation of alkaline phosphatase, HPO-CYFF-TPP converts to HO-CYFF-TPP and self-assembles into nanoparticles (NPs) with quenched fluorescent (FL) and opened photoacoustic (PA) signal. After laser irradiation, NPs can produce abundant singlet oxygen for photodynamic therapy (PDT) of tumor cells, which leading to the increase of intracellular viscosity. At high viscosity, NPs opens FL and further enhances PA signal. HPO-CY-TPP without self-assembly group is a control probe. HPO-CYFF-TPP or HPO-CY-TPP exhibits effective PDT against tumor cells and high tumor inhibition in tumor-bearing mice, while HPO-CYFF-TPP is more effective than HPO-CY-TPP due to the formation of NPs in situ. Importantly, HPO-CYFF-TPP or HPO-CY-TPP can monitor the viscosity during PDT on tumor cells and tumor-bearing mice for treatment feedback, while HPO-CYFF-TPP is more accurate than HPO-CY-TPP with higher FL/PA sensitivity. We envision that this self-assembled probe will be a powerful tool for tumor therapy and real-time treatment feedback imaging in the future.