Selective antibacterial and antibiofilm activity of chlorinated hemicyanine against gram-positive bacteria.

Antibiotic-free therapies are highly needed due to the limited success of conventional approaches especially against biofilm related infections. In this direction, antimicrobial phototherapy, either in the form of antimicrobial photothermal therapy (aPTT) or antimicrobial photodynamic therapy (aPDT), have appeared to be highly promising candidates in recent years. These are local and promising approaches for antibiotic resistant bacterial infections and biofilms.

Rechargeable Afterglow Nanotorches for In Vivo Tracing of Cell-Based Microrobots.

As one of the self-luminescence imaging approaches that require pre-illumination instead of real-time light excitation, afterglow luminescence imaging has attracted increasing enthusiasm to circumvent tissue autofluorescence. In this work, we developed organic afterglow luminescent nanoprobe (nanotorch), which could emit persistent luminescence more than 10 days upon single light excitation. More importantly, the nanotorch could be remote charged by 660 nm light in a non-invasive manner, which showed great potential for real-time tracing the location of macrophage cell-based microrobots.

Optical imaging probes for selective detection of butyrylcholinesterase.

Butyrylcholinesterase (BChE), a member of the human serine hydrolase family, is an essential enzyme for cholinergic neurotransmission as it catalyzes the hydrolysis of acetylcholine. It also plays central roles in apoptosis, lipid metabolism, and xenobiotic detoxification. On the other side, abnormal levels of BChE are directly associated with the formation of pathogenic states such as neurodegenerative diseases, psychiatric and cardiovascular disorders, liver damage, diabetes, and cancer.

A mitochondria-targeted chemiluminescent probe for detection of hydrogen sulfide in cancer cells, human serum and .

Hydrogen sulfide (HS) as a critical messenger molecule plays vital roles in regular cell function. However, abnormal levels of HS, especially mitochondrial HS, are directly correlated with the formation of pathological states including neurodegenerative diseases, cardiovascular disorders, and cancer. Thus, monitoring fluxes of mitochondrial HS concentrations both and with high selectivity and sensitivity is crucial.

Hydrogen Sulfide Responsive Phototherapy Agents: Design Strategies and Biological Applications.

Hydrogen sulfide (HS) is one of the critical gasotransmitters, which play important roles in regular physiological processes, especially in vital signaling pathways. However, fluctuations in endogenous HS concentration can be linked to serious health problems, such as neurodegenerative diseases, cancer, diabetes, inflammation, cardiovascular diseases, and hypertension. Thus, it has attracted a great deal of attention in therapeutic applications, specifically in the field of phototherapy.

A hydrogen sulfide and tyrosinase responsive dual-locked fluorophore for selective imaging of melanoma cells.

A resorufin-based dual-locked fluorescent probe (RHT) was introduced to image melanoma cells selectively. RHT was shown to function as an AND molecular logic gate as it emitted a signal only in the presence of both hydrogen sulfide (HS) and tyrosinase (Tyr), which are known to be overexpressed in melanoma cells. cell culture studies revealed that RHT can be activated with endogenous HS and Tyr and allows selective imaging of B16-F10 cancer cells under confocal microscopy.

Real-time visualization of butyrylcholinesterase activity using a highly selective and sensitive chemiluminescent probe.

Butyrylcholinesterase (BChE), one of the critical human cholinesterases, plays crucial roles in numerous physiological and pathological processes. Accordingly, it is a striking and at the same time challenging target for bioimaging studies. Herein, we developed the first ever example of a 1,2-dixoetane-based chemiluminescent probe (BCC) for monitoring BChE activity in native biological contexts such as living cells and animals.

Image-Guided Enhanced PDT/PTT Combination Therapy Using Brominated Hemicyanine-Loaded Folate Receptor-Targeting AgS Quantum Dots.

Tumor-targeting nanoparticles and phototherapies are the two major trends in tumor-specific, local cancer therapy with minimal side effects. Organic photosensitizers (PSs) usually offer effective photodynamic therapy (PDT) but require enhanced solubility and tumor-targeting, which may be provided by a nanoparticle. Near-infrared (NIR)-emitting AgS quantum dots may act as a delivery vehicle for the PS, NIR tracking agent, and as a phototherapy (PTT) agent.

Selenophene-Modified Boron Dipyrromethene-Based Photosensitizers Exhibit Photodynamic Inhibition on a Broad Range of Bacteria.

Microorganisms are crucial for human survival in view of both mutualistic and pathogen interactions. The control of the balance could be achieved by use of the antibiotics. There is a continuous arms race that exists between the pathogen and the antibiotics.

Selective detection of carboxylesterase 2 activity in cancer cells using an activity-based chemiluminescent probe.

Carboxylesterase 2 (CES2) has crucial roles in both xenobiotic metabolism and formation of pathogenic states including cancer. Thus, it is highly critical to monitor intracellular CES2 activity in living cancer cells. Here, we report a CES2 activatable phenoxy 1,2-dioxetane based chemiluminescent agent (CL-CES2).

Locked and Loaded: β-Galactosidase Activated Photodynamic Therapy Agent Enables Selective Imaging and Targeted Treatment of Glioblastoma Multiforme Cancer Cells.

Selective detection and effective therapy of brain cancer, specifically, the very aggressive glioblastoma multiforme (GBM), remains one of the paramount challenges in clinical settings. While radiotherapy combined surgery is proposed as the main treatment course, it has several drawbacks such as complexity of the operation and common development of recurrent tumors in this course of patient care. Unique opportunities presented by photodynamic therapy (PDT) offer promising, effective, and precise therapy against GBM cells along with simultaneous imaging opportunities.

Activity-Based Photosensitizers with Optimized Triplet State Characteristics Toward Cancer Cell Selective and Image Guided Photodynamic Therapy.

Activity-based theranostic photosensitizers are highly attractive in photodynamic therapy as they offer enhanced therapeutic outcome on cancer cells with an imaging opportunity at the same time. However, photosensitizers (PS) cores that can be easily converted to activity-based photosensitizers (aPSs) are still quite limited in the literature. In this study, we modified the dicyanomethylene-4-chromene (DCM) core with a heavy iodine atom to get two different PSs (DCM-I, I-DCM-Cl) that can be further converted to aPS after simple modifications.

Development of a cysteine responsive chlorinated hemicyanine for image-guided dual phototherapy.

A cysteine (Cys) activatable chlorinated hemicyanine (Cl-Cys) was introduced as a tumour selective image-guided dual phototherapy agent. Cl-Cys exhibited a significant turn on response in its near-IR emission signal and activated its singlet oxygen generation as well as photothermal conversion potentials upon reacting with Cys. The laser irradiation of Cl-Cys induced significant cell death in cancer cells with high Cys level, while it stayed deactivated and non-emissive in a healthy cell line.

Recent Advances in Cyanine-Based Phototherapy Agents.

Phototherapies, in the form of photodynamic therapy (PDT) and photothermal therapy (PTT), are very promising treatment modalities for cancer since they provide locality and turn-on mechanism for toxicity, both of which are critical in reducing off-site toxicity. Irradiation of photosensitive agents demonstrated successful therapeutic outcomes; however, each approach has its limitations and needs to be improved for clinical success. The combination of PTT and PDT may work in a synergistic way to overcome the limitations of each method and indeed improve the treatment efficacy.

Balanced Intersystem Crossing in Iodinated Silicon-Fluoresceins Allows New Class of Red Shifted Theranostic Agents.

Iodination of the silicon-fluorescein core revealed a new class of highly cytotoxic, red-shifted and water-soluble photosensitizer (SF-I) which is also fairly emissive to serve as a theranostic agent. Singlet oxygen generation capacity of SF-I was evaluated chemically, and up to 45% singlet oxygen quantum yield was reported in aqueous solutions. SF-I was further tested in triple negative breast (MDA MB-231) and colon (HCT-116) cancer cell lines, which are known to have limited chemotherapy options as well as very poor prognosis.

Dual laser activatable brominated hemicyanine as a highly efficient and photostable multimodal phototherapy agent.

Dual phototherapy agents have attracted great interest in recent years as they offer enhanced cytotoxicity on cancer cells due to the synergistic effect of photodynamic and photothermal therapies (PDT/PTT). In this study, we demonstrate a brominated hemicyanine (HC-1), which is previously shown as mitochondria targeting PDT agent, can also serve as an effective photosensitizer for PTT for the first time under a single (640 nm or 808 nm) and dual laser (640 nm + 808 nm) irradiation. Generation of reactive oxygen species and photothermal conversion as a function of irradiation wavelength and power were studied.

Resorufin Enters the Photodynamic Therapy Arena: A Monoamine Oxidase Activatable Agent for Selective Cytotoxicity.

A red-absorbing, water-soluble, and iodinated resorufin derivative () that can be selectively activated with a monoamine oxidase (MAO) enzyme was synthesized, and its potential as a photodynamic therapy (PDT) agent was evaluated. showed high O generation yields in aqueous solutions upon addition of MAO isoforms, and it was further tested in cell culture studies. induced photocytotoxicity after being triggered by endogenous MAO enzyme in cancer cells with a much higher efficiency in SH-SY5Y neuroblastoma cells with high MAO-A expression.

Mitochondria-Targeting Selenophene-Modified BODIPY-Based Photosensitizers for the Treatment of Hypoxic Cancer Cells.

Two red-absorbing, water-soluble and mitochondria (MT)-targeting selenophene-substituted BODIPY-based photosensitizers (PSs) were realized (BOD-Se, BOD-Se-I), and their potential as photodynamic therapy (PDT) agents were evaluated. BOD-Se-I showed higher O generation yield thanks to the enhanced heavy-atom effect, and this derivative was further tested in detail in cell culture studies under both normoxic and hypoxic conditions. BOD-Se-I not only effectively functioned under hypoxic conditions, but also showed highly selective photocytotoxicity towards cancer cells.

Molecular logic gates: the past, present and future.

The field of molecular logic gates originated 25 years ago, when A. P. de Silva published a seminal article in Nature.

Tuning the Color Palette of Fluorescent Copper Sensors through Systematic Heteroatom Substitution at Rhodol Cores.

Copper is an essential nutrient for sustaining life, and emerging data have expanded the roles of this metal in biology from its canonical functions as a static enzyme cofactor to dynamic functions as a transition metal signal. At the same time, loosely bound, labile copper pools can trigger oxidative stress and damaging events that are detrimental if misregulated. The signal/stress dichotomy of copper motivates the development of new chemical tools to study its spatial and temporal distributions in native biological contexts such as living cells.

Thioether Coordination Chemistry for Molecular Imaging of Copper in Biological Systems.

Copper is an essential element in biological systems. Its potent redox activity renders it necessary for life, but at the same time, misregulation of its cellular pools can lead to oxidative stress implicated in aging and various disease states. Copper is commonly thought of as a static cofactor buried in protein active sites; however, evidence of a more loosely bound, labile pool of copper has emerged.

Remote-Controlled Release of Singlet Oxygen by the Plasmonic Heating of Endoperoxide-Modified Gold Nanorods: Towards a Paradigm Change in Photodynamic Therapy.

The photodynamic therapy of cancer is contingent upon the sustained generation of singlet oxygen in the tumor region. However, tumors of the most metastatic cancer types develop a region of severe hypoxia, which puts them beyond the reach of most therapeutic protocols. More troublesome, photodynamic action generates acute hypoxia as the process itself diminishes cellular oxygen reserves, which makes it a self-limiting method.

Intracellular modulation of excited-state dynamics in a chromophore dyad: differential enhancement of photocytotoxicity targeting cancer cells.

The photosensitized generation of reactive oxygen species, and particularly of singlet oxygen [O2 (a(1) Δg )], is the essence of photodynamic action exploited in photodynamic therapy. The ability to switch singlet oxygen generation on/off would be highly valuable, especially when it is linked to a cancer-related cellular parameter. Building on recent findings related to intersystem crossing efficiency, we designed a dimeric BODIPY dye with reduced symmetry, which is ineffective as a photosensitizer unless it is activated by a reaction with intracellular glutathione (GSH).

Designing an intracellular fluorescent probe for glutathione: two modulation sites for selective signal transduction.

A selective probe for glutathione was designed and synthesized. The design incorporates spatial and photophysical constraints for the maximal emission signal. Thus, pHs, as well as the intracellular thiol concentrations, determine the emission signal intensity through a tight control of charge-transfer and PeT processes.

Atropisomeric dyes: axial chirality in orthogonal BODIPY oligomers.

A dissymmetrically substituted orthogonal BODIPY dimer and an orthogonal BODIPY trimer exist as two stable conformers, which are in fact atropisomeric enantiomers. The racemic mixture can be separated by HPLC using a chiral stationary phase. These enantiomeric derivatives hold great potential as chiral agents in asymmetric synthesis, fluorogenic/chromogenic sensing, and biological applications.