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

Author:
Shen, Yizhong, Tian, Qian, Sun, Yidan, Xu, Jing-Juan, Ye, Deju, Chen, Hong-Yuan
Source:
Analytical chemistry 2017 v.89 no.24 pp. 13610-13617
ISSN:
1520-6882
Subject:
adenosine triphosphate, adverse effects, color, dissociation, emissions, endocytosis, fluorescence, image analysis, mice, micelles, monitoring, nanoparticles, neoplasm cells, neoplasms, oligonucleotides, photochemotherapy, photosensitizing agents
Abstract:
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.
Agid:
5951629