Photo-controlled Manner Research Articles

A switchable zinc-based metal organic framework for the light triggered absorption and release of organic dyes

Due to its adjustable pore structure, the metal–organic frameworks (MOFs) have attracted much attention in the treatment of organic dye molecules in wastewater. However, the general tuning of the pore channels of MOFs is mainly by changing the chain length of the organic ligands and metal nodes. This approach not only limits the types of MOFs, but also limits the treatment of a large number of dye methylene blue (MB) and methyl orange (MO) dye molecules in the wastewater. Hence, we synthesized photoresponsive Zn-AzDC/TPA MOF as adsorbents to adsorb and release organic dye molecules in a photo-controlled manner. The photoresponsive Zn-AzDC/TPA was prepared using a mixed ligand strategy, in which the azobenzene carboxylic acid derivative (AzDC) served as a photoresponsive ligand and terephthalic acid (TPA) served as a non-active ligand in coordination with zinc ion. The optical and structural properties of the synthesized Zn-AzDC/TPA was characterized by UV–vis, FT-IR, PXRD, SEM, TEM, TGA, and pore analysis. Interestingly, it was found that the photoresponsive AzDC unit of Zn-AzDC/TPA demonstrated reversible trans–cis isomerization under the alternating UV and visible light, resulting in reversible changes in the pore size of the Zn-AzDC/TPA. Its photoresponse properties can trapp and release dye molecules under light-driven conditions. This result provides a new direction for the application of photoresponsive MOF and also lays a foundation for the study of diversified optically responsive materials.

Bifunctional chimera for ligand-directed photo-degradation of oncogenic microRNA.

Targeted inhibition of oncogenic microRNAs provides a promising anti-cancer approach. Here, we report a bifunctional chimera for ligand-directed regulation of target oncogenic precursor microRNA through photo-degradation. Chimeric TGP-210-Ppa with photosensitizer pyropheophorbide a (Ppa) linked with the ligand of the oncogenic precursor miR-210 was able to bind specifically to oncogenIc pre-miRNA and produce 1O2 under red light irradiation to degrade the target pre-miRNA. This bifunctional chimera-based modification of precursor microRNA serves as a unique method for target gene regulation since photo-irradiation was able to provide temporal-spatial resolution. We demonstrated that TGP-210-Ppa prevented the generation of functional miR-210 in breast cancer cells in a photocontrollable manner. This also successfully reversed the downstream oncogenic signaling pathway mediated by miR-210 to promote cancer cell death.

A photosensitizing perylenediimide dye lights up cell nucleolus through visible light-mediated intracellular translocation

Intracellular redistribution of a photosensitizing fluorescent dye is concerned with its diagnostic and therapeutic features. To date such studies in this area are extremely scarce. Herein, a fluorescent photosensitizer PDI-1 with lysosome-targeting function has been prepared by functionalization of perylenediimide (PDI) with bis-tertiary amine groups. Fluorescence live cell imaging shows that PDI-1 can indeed target the lysosome, however, uncommon inter-organelle translocation was observed under continual visible light irradiation through a microscope. The cell nucleolus was subsequently lit up by PDI-1 in a photo-controllable manner. The imaging study using fixed cells confirmed that RNAs were the major target of PDI-1 in cell nucleolus. In addition, PDI-2 and PDI-3 were prepared by slightly modifying the structure of PDI-1. However, there is no obvious photo-induced redistribution observed on both PDI-2 and PDI-3. The result implies that even though tiny modification to the structure of a photosensitizer, the influence can be significant for its photobiological behavior.

Photo-controllability of fluoride remediation by spiropyran-functionalized mesoporous silica powder

Fluoride contamination in water continues to be a great challenge to the sustainable development of global fluorine-containing industries. It is still a challenge to avoid the use of chemical desorbents induced secondary contamination in regenerating fluoride adsorbents. In this work, we aim to design a nanoadsorbent (SP@SiO2) specifically applicable for fluoride (F−) adsorption and desorption without using chemical desorbents, but via the approach of light-induction. The SP@SiO2 was fabricated by conjugating a rationally synthesised light-sensitive compound, spiropyran (SP), onto engineered mesoporous silica (SiO2) nanoparticles. Results showed that there was ∼0.14-0.15 mmol of SP conjugated onto per g of nanocomposite surface, forming a core-shell structure, which can realize conformational freedom of SP ↔ MC (merocyanine) transformation and corresponding adsorption and desorption fluoride under photo-controllable manner. Based on these, we intend to engineer a nanoadsorbent for F− remediation that may be potential guidance for those poisonous anions adsorption and light-induced desorption based on spiropyran-functionalized materials.

Systematic investigation of bioorthogonal cellular DNA metabolic labeling in a photo-controlled manner

Bioorthogonal cleavage and ligation reactions together form one more integrated system about the repertoire of bioorthogonal chemistry, capacitating an array of thrilling new biological applications. The bond-cleavage type and position of biomolecular remain a great challenge, which determines the metabolic pathway of the targets in living systems. Herein we designed two linkages of methylene and carbonyl group attached the N-3 position of the 5-ethynyl-2′-deoxyuridine (EdU) base or the oxygen atom at deoxyribose 3′ position to a photocaging group, which would be cleaved by irradiation with 365 nm ultraviolet light. EdU derivatives linked by methylene at the N-3 position had better photodecage efficiency and stability in the absence of light. This paper provides a strategy for studying the nucleoside metabolic pathways in cells, which can easily and conveniently evaluate the effect of the position and type of the linkages. The developed strategy affords a reference for controlling spatial and temporal metabolism of small-molecule drugs, allowing direct manipulation of intact cells under physiological conditions.

In Situ Photoconversion of Multicolor Luminescence and Pure White Light Emission Based on Carbon Dot-Supported Supramolecular Assembly.

Constructing multicolor photoluminescence materials that allow for the integration of suitable external stimuli in order to control luminescence color conversions is a challenging objective. Multicolor luminescent output that is regulated in an in situ photo-controlled manner is not a common phenomenon. Herein, a photoluminescent supramolecular assembly, prepared in two stages, is described that displays in situ photo-tuning broad-spectrum output. Benefiting from the reversible photo-switched constitutional interconversion of diarylethenes, the fluorescence of a guest molecule, styrylpyridinium-modified diarylethene, can be switched on/off by alternating ultraviolet and visible light irradiation. Upon complexation of this guest with a host, cucurbit[8]uril, the fluorescence intensity of the resulting binary supramolecular nanofiber shows a drastic enhancement when compared with that of the free guest, which can also be quenched and recovered reversibly by light irradiation. Significantly, such cationic supramolecular nanofibers also interact with anionic carbon dots to form broad-spectrum output ternary supramolecular assemblies, the fluorescence of which can be changed efficiently from yellow to blue in an in situ photo-controlled manner. Pure white light emission can be realized expediently in the luminescence color-conversion process. The use of light as an external stimulus to regulate fluorescent color conversion provides us with an opportunity to design and construct more advanced anti-counterfeiting materials as well as visual display instruments.

Two-dimensional supramolecular assemblies based on β-cyclodextrin-grafted graphene oxide for mitochondrial dysfunction and photothermal therapy.

β-Cyclodextrin (CD)-grafted graphene oxide (GO) is an emerging drug carrier for human diseases therapy. Herein, we report two-dimensional nano-supramolecular assemblies to specifically target and disrupt tumor cell mitochondria in a photocontrollable manner. Moreover, the nanoassemblies displayed extremely high near-infrared-induced photothermal efficiency.

A Light-Controlled Allosteric Modulator Unveils a Role for mGlu4 Receptors During Early Stages of Ischemia in the Rodent Cerebellar Cortex.

Metabotropic glutamate receptors (mGlus) are G Protein coupled-receptors that modulate synaptic transmission and plasticity in the central nervous system. Some act as autoreceptors to control neurotransmitter release at excitatory synapses and have become attractive targets for drug therapy to treat certain neurological disorders. However, the high degree of sequence conservation around the glutamate binding site makes the development of subtype-specific orthosteric ligands difficult to achieve. This problem can be circumvented by designing molecules that target specific less well conserved allosteric sites. One such allosteric drug, the photo-switchable compound OptoGluNAM4.1, has been recently employed to reversibly inhibit the activity of metabotropic glutamate 4 (mGlu4) receptors in cell cultures and in vivo. We studied OptoGluNAM4.1 as a negative modulator of neurotransmission in rodent cerebellar slices at the parallel fiber – Purkinje cell synapse. Our data show that OptoGluNAM4.1 antagonizes pharmacological activation of mGlu4 receptors in a fully reversible and photo-controllable manner. In addition, for the first time, this new allosteric modulator allowed us to demonstrate that, in brain slices from the rodent cerebellar cortex, mGlu4 receptors are endogenously activated in excitotoxic conditions, such as the early phases of simulated cerebellar ischemia, which is associated with elevated levels of extracellular glutamate. These findings support OptoGluNAM4.1 as a promising new tool for unraveling the role of mGlu4 receptors in the central nervous system in physio-pathological conditions.

A Smart, Photocontrollable Drug Release Nanosystem for Multifunctional Synergistic Cancer Therapy.

Multifunctional synergistic therapy holds promise in biomedical studies and clinical practice. However, strategies aimed at easily integrating the components of such multimodal therapies are needed. Therefore, we herein report a smart drug release nanosystem able to perform photodynamic therapy, photothermal therapy and chemotherapy in a photocontrollable manner. Doxorubicin (DOX), a chemotherapy drug, and 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4), a photosensitizer, were physically intercalated into a DNA assembly immobilized on gold nanorods. The drugs were efficiently delivered to target cells and released under light irradiation, resulting in a synergism that combined phototherapy and chemotherapy for cancer treatment. This smart, photocontrollable drug release nanosystem promises precisely controlled drug release for multifunctional synergistic cancer therapy.

Allosteric Inhibitory Molecular Recognition of a Photochromic Dye by a Digestive Enzyme: Dihydroindolizine makes α-chymotrypsin Photo-responsive.

The structural-functional regulation of enzymes by the administration of an external stimulus such as light could create photo-switches that exhibit unique biotechnological applications. However, molecular recognition of small ligands is a central phenomenon involved in all biological processes. We demonstrate herein that the molecular recognition of a photochromic ligand, dihydroindolizine (DHI), by serine protease α-chymotrypsin (CHT) leads to the photo-control of enzymatic activity. We synthesized and optically characterized the photochromic DHI. Light-induced reversible pyrroline ring opening and a consequent thermal back reaction via 1,5-electrocyclization are responsible for the photochromic behavior. Furthermore, DHI inhibits the enzymatic activity of CHT in a photo-controlled manner. Simultaneous binding of the well-known inhibitors 4-nitrophenyl anthranilate (NPA) or proflavin (PF) in the presence of DHI displays spectral overlap between the emission of CHT-NPA or CHT-PF with the respective absorption of cis or trans DHI. The results suggest an opportunity to explore the binding site of DHI using Förster resonance energy transfer (FRET). Moreover, to more specifically evaluate the DHI binding interactions, we employed molecular docking calculations, which suggested binding near the hydrophobic site of Cys-1-Cys-122 residues. Variations in the electrostatic interactions of the two conformers of DHI adopt unfavorable conformations, leading to the allosteric inhibition of enzymatic activity.

Photoreversible [2] Catenane via the Host–Guest Interactions between a Palladium Metallacycle and β-Cyclodextrin

We report the efficient preparation of an A2D2 (A = acceptor and D = donor) metallacycle 2 = [(en)2Pd2(1)2](NO3)4, using the coordination driven self-assembly of trans-azobenzene based bispyridyl ligand 1 and (en)Pd(NO3)2 (en = ethylenediamine). In the metallacycle, the trans-azobenzene units serve both as a structural element and as sites for subsequent host-guest chemistry with β-cyclodextrin, leading to the formation of a [2] catenane 3. This catenation process is reversible and can be switched off and on in a photocontrollable manner via the trans-cis isomerization of the azobenzene units.

Automated Modular Synthesis of Aptamer–Drug Conjugates for Targeted Drug Delivery

Aptamer–drug conjugates (ApDCs) are promising targeted drug delivery systems for reducing toxicity while increasing the efficacy of chemotherapy. However, current ApDC technologies suffer from problems caused by the complicated preparation and low controllability of drug–aptamer conjugation. To solve such problems, we have designed and synthesized a therapeutic module for solid phase synthesis, which is a phosphoramdite containing an anticancer drug moiety and a photocleavable linker. Using this module, we have realized automated and modular synthesis of ApDCs, and multiple drugs were efficiently incorporated into ApDCs at predesigned positions. The ApDCs not only recognize target cancer cells specifically, but also release drugs in a photocontrollable manner. We demonstrated the potential of automated and modular ApDC technology for applications in targeted cancer therapy.

PEGylated Polymer Micelle-based Nitric Oxide (NO) Photodonor with NO-mediated Antitumor Activity

Abstract PEGylated polymer micelles containing 4-nitro-3-trifluoromethylphenyl units within the core moiety were prepared, and their phototriggered nitric oxide (NO)-generating ability was confirmed by electron spin resonance (ESR) spin-trapping and the Griess method. These micelles were found to be capable of delivering exogenous NO into tumor cells in a photocontrolled manner and showed an NO-mediated antitumor effect, indicating the usability of this molecular system in NO-based tumor therapy.