Near‐Infrared Photothermally Activated DNAzyme–Gold Nanoshells for Imaging Metal Ions in Living Cells

Abstract

DNAzymes have enjoyed success as metal ion sensors outside cells. Their susceptibility to metal-dependent cleavage during delivery into cells has limited their intracellular applications. To overcome this limitation, we herein report a near-infrared (NIR) photothermal activation method for controlling DNAzyme activity in living cells. The system consists of a three-stranded DNAzyme precursor (TSDP) whose hybridization prevents the DNAzyme from being active. After conjugating the TSDP onto gold nanoshells and upon NIR illumination, the increased temperature dehybridizes the TSDP to release the active DNAzyme, which then carries out metal ion-dependent cleavage, resulting in releasing the cleaved product containing a fluorophore. Using this construct, detecting Zn2+ in living HeLa cells is demonstrated. This method has expanded the DNAzyme versatility for detecting metal ions in biological systems under NIR light that exhibits lower phototoxicity and higher tissue penetration ability.

Nucleic‐Acid Structures as Intracellular Probes for Live Cells

“…One limitation of DNAzymes is metal‐dependent degradation prior to intracellular entry. As a potential solution to this problem, Wang et al developed NIR activated DNAzymes . Gold nanoshells were functionalized with a three‐stranded DNAzyme precursor.…”

DNAzymes: Selected for Applications

“…Although in theory RNA‐cleaving DNAzymes can also be used as intracellular sensors, a significant challenge is its “always‐on” property, which is not compatible with the often “on‐demand” nature of intracellular sensing: detecting an analyte at a specific time or under a specific change of conditions. Yi Lu's group has solved this issue by using a photoactivated version of RNA‐cleaving DNAzymes . Their design was based on the fact that most RNA‐cleaving DNAzymes cleave the targeted phosphodiester bond using the widely known transesterification mechanism—the 2′‐hydroxyl group at the cleavage site is used as the nucleophile to attach the nearby phosphodiester bond.…”

“…The photoactivation is also achieved using an alternative strategy: conjugation to gold nanoshells that can produce heat upon irradiation with a near‐infrared light. The increased temperature causes the release of the DNAzyme from the deactivating DNA complex . The advantage of using a near‐infrared wavelength to control DNAzyme activity in living cells is that it exhibits lower phototoxicity, while at the same time affording higher tissue‐penetration ability than UV light.…”

Environment‐Recognizing DNA‐Computation Circuits for the Intracellular Transport of Molecular Payloads for mRNA Imaging

“…However, the activation of the FNA nanocarriers in vivo for controllable cargo release once they enter cells remains a challenge. The photochemical caging strategy is a widely used external trigger mechanism, which usually relies on UV‐light irradiation with high phototoxicity and low tissue penetration. To overcome these troubles, here we seek to employ endogenous cellular components instead of external stimuli to activate FNA nanocarriers in situ and unload molecular payloads logically controlled by cellular environment‐responsive DNA‐computation circuits.…”