Remote Regulation of Membrane Channel Activity by Site‐Specific Localization of Lanthanide‐Doped Upconversion Nanocrystals

Abstract

The spatiotemporal regulation of light-gated ion channels is a powerful tool to study physiological pathways and develop personalized theranostic modalities. So far, most existing light-gated channels are limited by their action spectra in the ultraviolet (UV) or visible region. Simple and innovative strategies for the specific attachment of photoswitches on the cell surface without modifying or genetically encoding channel structures, and more importantly, that enable the remote activation of ion-channel functions within near-infrared (NIR) spectral window in living systems, remain a challenging concern. Herein, metabolic glycan biosynthesis is used to achieve site-specific covalent attachment of near-infrared-light-mediated lanthanide-doped upconversion nanocrystals (UCNs) to the cell surface through copper-free click cyclization. Upon irradiation with 808 nm light, the converted emission at 480 nm could activate a light-gated ion channel, channelrhodopsins-2 (ChR2), and thus remotely control the cation influx. This unique strategy provides valuable insights on the specific regulation membrane-associated activities in vivo.

Near‐Infrared Light Activated Thermosensitive Ion Channel to Remotely Control Transgene System for Thrombolysis Therapy

“…Next, to effectively attach the nanotransducer onto the surface of engineered cell membrane, a metabolic glycoengineering approach was performed according to previously reported literatures . As shown in Figure f, the PMSF‐DyLight with red fluorescence could effectively surround the membrane of TRPV1 overexpressed HEK293T cells (Figure S6, Supporting Information).…”

Advanced Bottom‐Up Engineering of Living Architectures

“…When envisioning the generation of nanoenabled cell clusters for tissue engineering, avoiding intracellular uptake is a critical parameter. To this end, photoswitchable nanoparticles were covalently bound to living cell membranes via a similar glycoengineering strategy . Site‐specific membrane localization of upconversion nanoparticles in human embryonic kidney 293 (HEK293) cells was evident in fluorescence microscopy studies, which inspires future studies where spatial bioactive presentation can be tuned by external triggers and achieve localized differentiation in hierarchic constructs.…”

A DNA–Azobenzene Nanopump Fueled by Upconversion Luminescence for Controllable Intracellular Drug Release

“…[2] Stimulus-responsive drug-release systems can enhance drug accumulation in tumor tissues and eliminate off-target toxicity. [2b, 3] Azobenzene (azo), which can reversibly isomerizes between cis and trans form under visible (Vis) and UV irradiation, [4] has been assembled on the surface of mesoporous nanoparticles [5] and microporous multilayer films [6] to act as ap hotoresponsive trigger for controlled drug release.To improve release efficiency, some pump-type switchers [7,8] have been designed to accelerate the drug-release process.W ith the capability of simultaneously emitting photons in both UV and Visr egions upon near-infrared (NIR) irradiation, [9] upconversion nanoparticles (UCNPs) have been modified with azo [10] to continuously transform azo back and forth to propel drug release. [10a] In these UCNPs-azo nanodevices, [4a, 10] azo is usually isolated from UCNPs,w hich weakens the luminescence-fueled efficiency.Therefore,these strategies need al ong exposure time to release ad rug in asatisfactory amount, which results in at hermal injury from continuous point-fixed irradiation.To overcome this drawback, this work used azo-functionalized DNAs trands to design an anopump for efficient and controllable drug release.F lexible DNAc hains could be compactly assembled on UCNPs [11] to act as the pump-type switcher triggered by the reversible conformational change of azo,w hich is conveniently fueled by Visa nd UV irradiation emitted from the UCNPs.M oreover,t he anticancer drug doxorubicin (DOX) could be selectively intercalated in as pecific DNAh elix [12] for highly efficient loading (Scheme 1a).…”

“…To improve release efficiency, some pump-type switchers [7,8] have been designed to accelerate the drug-release process.W ith the capability of simultaneously emitting photons in both UV and Visr egions upon near-infrared (NIR) irradiation, [9] upconversion nanoparticles (UCNPs) have been modified with azo [10] to continuously transform azo back and forth to propel drug release. [10a] In these UCNPs-azo nanodevices, [4a, 10] azo is usually isolated from UCNPs,w hich weakens the luminescence-fueled efficiency.Therefore,these strategies need al ong exposure time to release ad rug in asatisfactory amount, which results in at hermal injury from continuous point-fixed irradiation.…”