Reductase and Light Programmatical Gated DNA Nanodevice for Spatiotemporally Controlled Imaging of Biomolecules in Subcellular Organelles under Hypoxic Conditions

Abstract

Monitoring hypoxia-related changes in subcellular organelles would provide deeper insights into hypoxia-related metabolic pathways, further helping us to recognize various diseases on subcellular level. However, there is still a lack of real-time, in situ, and controllable means for biosensing in subcellular organelles under hypoxic conditions. Herein, we report a reductase and light programmatical gated nanodevice via integrating light-responsive DNA probes into a hypoxia-responsive metal–organic framework for spatiotemporally controlled imaging of biomolecules in subcellular organelles under hypoxic conditions. A small-molecule-decorated strategy was applied to endow the nanodevice with the ability to target subcellular organelles. Dynamic changes of mitochondrial adenosine triphosphate under hypoxic conditions were chosen as a model physiological process. The assay was validated in living cells and tumor tissue slices obtained from mice models. Due to the highly integrated, easily accessible, and available for living cells and tissues, we envision that the concept and methodology can be further extended to monitor biomolecules in other subcellular organelles under hypoxic conditions with a spatiotemporal controllable approach.

Advances and prospects of dynamic DNA nanostructures in biomedical applications

“…2A ). 55 This study bridges the gap between spatial and temporal controlled imaging studies of biomolecules in organelles under hypoxic conditions. By detecting histological changes associated with hypoxia at the organelle level, researchers can increase their understanding of hypoxia-related metabolic pathways.…”

“…(A) Design of spatiotemporally controlled nanodevice and its mechanism in the visualization of ATP in mitochondria under hypoxic conditions. Reproduced with permission 55. Copyright 2021, American Chemical Society.…”

Subcellular localization of DNA nanodevices and their applications

“…Liu et al combined cyanine dyes with a Y-shaped acid aptamer to achieve sensing and imaging of ATP in the mitochondria of living cells. 82 Luo et al hybridized two hairpin DNA strands (HS1-Cy3 and HS2-Cy5) containing multiple ATP aptamer fragments. When ATP combined with the aptamer fragments on the DNA double-strand, the distance between Cy3 and Cy5 was shortened and a FRET signal was generated, resulting in ratio imaging of ATP in the mitochondria (Fig.…”

An azoreductase activatable, endonuclease-gated nanodevice for spatiotemporal amplification imaging of microRNA-21 in hypoxic tumor cells

“…AMOF was then synthesized by a one-pot method. 15 The characterization of transmission electron microscopy (TEM) shows that the morphology of AMOF is rod-shaped, around 96.2 AE 9.2 nm in length and 14.7 AE 2.3 nm in width (Fig. S9A, ESI †).…”