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Engineering of ATP-Powered Photosensitizer for Targeted Recycling Activatable Imaging of MicroRNA and Controllable Cascade Amplification Photodynamic Therapy

Author:
Shen, Yizhong, Wu, Tingting, Tian, Qian, Mao, Yu, Hu, Junjie, Luo, Xiliang, Ye, Yingwang, Chen, Hong-Yuan, Xu, Jing-Juan
Source:
Analytical chemistry 2019 v.91 no.12 pp. 7879-7886
ISSN:
1520-6882
Subject:
DNA, adverse effects, dissociation, emissions, endocytosis, engineering, fluorescence, folic acid, image analysis, mice, micelles, microRNA, nanoparticles, neoplasm cells, neoplasms, oligonucleotides, photochemotherapy, photosensitizing agents
Abstract:
Owing to the low abundance of microRNAs (miRNAs) in living tumor cells, the development of intracellular cancer-relevant miRNA stimuli-activatable photosensitizers (PSs) for accurate imaging and efficient photodynamic therapy (PDT) of tumors in vivo is extremely challenging. Herein, we engineered a tumor targeting and intracellular trace miRNA-activatable nanophotosensitizer Y-motif/FA@HyNP on the basis of an endogenous ATP-powered strand-displacement cascade amplification strategy, which was prepared by assembly of a quencher BHQ₂-labeled Y-motif DNA structure (containing ATP-binding aptamer and target miRNA-binding complementary sequence) on the surface of folate (FA) and amine-functionalized hybrid micellar nanoparticles. We showed that the fluorescence emissions at both 555 and 627 nm were effectively inhibited due to BHQ₂ in Y-motif/FA@HyNPs, leading to negligible PDT efficacy. Once Y-motif/FA@HyNPs were selectively internalized into tumor cells via FA-receptor-mediated endocytosis, the intracellular trace target miRNA initiated the dissociation of the BHQ₂-terminated sequences from Y-motif/FA@HyNPs by means of abundant endogenous ATP-powered strand-displacement reactions, causing remarkable fluorescence enhancement and cascade amplification PDT. The activated dual-color fluorescence emissions at 555 and 627 nm were feasible to achieve real-time, highly sensitive, and specific imaging of trace target miRNA in living tumor cells. With the guidance of excellent imaging in living mice, Y-motif/FA@HyNPs exhibited the precise and efficient PDT of tumors as well as insignificant side effects in vivo. This work revealed the great potential of using an integration of receptor-mediated cell uptake and target-triggered recycling cascade amplification strategy to design early cancer-relevant stimuli-activatable PSs for both fluorescence imaging and PDT ablation of tumors in vivo, which could effectively facilitate the timeliness and precision of early cancer diagnosis and therapy.
Agid:
6472546