ABSTRACT
Rational manipulation of nonradiative decay channels is of crucial significance to improve photothermal conversion efficiency (PCE) and design photothermal agents. We first used the "internal and external combined" nonradiative decay strategy to enhance PCE. Specifically, organic IR-Y6 NPs with strong NIR absorption and high molar extinction coefficient were prepared and characterized. By means of TD-DFT calculations and fs-TA spectroscopy, the dual nonradiative decay channels composed of the free rotor (external strategy) and ultrafast dark excited states (DESs) between S0 and S1 states (internal strategy) were proved, which significantly enhanced PCE, up to 66%. IR-Y6 NPs were applied to a mice tumor model for photoacoustic image-guided photothermal therapy, showing complete tumor ablation ability and good biocompatibility for the normal organs. This work is of significance to deeply understand the nonradiation decay mechanism and rational design of high-performance PTT agents.
Subject(s)
Antineoplastic Agents/therapeutic use , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Indans/therapeutic use , Nanoparticles/therapeutic use , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/radiation effects , Cell Line, Tumor , Combined Modality Therapy , Density Functional Theory , Female , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Heterocyclic Compounds, 4 or More Rings/radiation effects , Humans , Indans/chemical synthesis , Indans/radiation effects , Infrared Rays , Mice, Inbred BALB C , Models, Chemical , Nanoparticles/chemistry , Nanoparticles/radiation effects , Photoacoustic Techniques , Photothermal Therapy , Theranostic Nanomedicine/methodsABSTRACT
A cyclocyanine (CC)-based organic small molecule two-photon (TP) fluorescent probe (CCNa1) was developed for mitochondrial sodium ion sensing. CCNa1 exhibits a low solvatochromic shift and strong TP fluorescence enhancement at 575 nm upon binding to Na+ and is insensitive to other metal ions and to pH. CCNa1 demonstrated fast cell loading ability, biocompatibility, and sensitive response to mitochondrial Na+ influx in live cells and mouse brain tissue.
Subject(s)
Fluorescent Dyes/chemistry , Mitochondria/chemistry , Sodium/analysis , Animals , Crown Ethers/chemistry , Crown Ethers/radiation effects , Crown Ethers/toxicity , Fluorescent Dyes/radiation effects , Fluorescent Dyes/toxicity , HeLa Cells , Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/radiation effects , Heterocyclic Compounds, 4 or More Rings/toxicity , Hippocampus/metabolism , Humans , Mice , Photons , Sodium/metabolismABSTRACT
Blebbistatin was recently identified as a selective, cell-permeant inhibitor of myosin II. Because blebbistatin is likely to be used extensively with fluorescence imaging in studies of cytoskeletal dynamics, its compatibility with common excitation wavelengths was examined. Illumination of blebbistatin-treated bovine aortic endothelial cells at 365 and 450-490 nm, but not 510-560 or 590-650 nm, caused dose-dependent cell death. Illumination of blebbistatin alone at 365 and 450-490 nm changed its absorption and emission spectra, but the resultant compounds were not toxic. In addition, photoreacted blebbistatin no longer disrupted myosin distribution in cells, indicating loss of pharmacological activity. Fluorescence microscopy showed that upon illumination, blebbistatin became bound to cells and to protein-coated glass, suggesting that toxicity may arise from light-induced reaction of blebbistatin with cell proteins. Blebbistatin should be used only with careful consideration of these photochemical effects.
Subject(s)
Endothelium, Vascular/drug effects , Endothelium, Vascular/radiation effects , Heterocyclic Compounds, 4 or More Rings/radiation effects , Heterocyclic Compounds, 4 or More Rings/toxicity , Light , Ultraviolet Rays , Animals , Aorta/cytology , Aorta/drug effects , Aorta/radiation effects , Cattle , Cells, Cultured , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Drug Resistance/radiation effects , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Heterocyclic Compounds, 4 or More Rings/pharmacokinetics , Radiation Tolerance/drug effects , Tissue DistributionABSTRACT
As a novel type of regulator molecule for DNA-recognizing proteins, a photo-cross-linked oligonucleotide duplex was designed and synthesized. The molecule regulated the activity of a restriction endonuclease by being recognized as a substrate. This type of regulating molecule is regarded as a decoy-DNA. 4,5',8-[4-Aminoethylaminomethyl]-trioxalen (aeAMT) was conjugated with an oligodeoxyribonucleotide (ODN) at the 5'-end and the aeAMT was cross-linked with the thymine residue of the complementary oligonucleotide upon UVA irradiation. The terminally cross-linked oligonucleotides, singly clipped (SC) decoy-DNA, acquired thermal stability. An oligonucleoside phosphorothioate (OPT) was also introduced as one or both components, yielding three types of decoy-DNAs, SC-ODN-ODN (SC.DD), SC-OPT-ODN (SC.SD), and SC-OPT-OPT (SC.SS). The SC decoy-DNAs inhibited the function of the restriction endonuclease, AatII, in a sequence-specific and concentration-dependent manner with an appreciable IC50 value (1.3 microM for SC.DD, 0.016 microM for SC.SD, 0.002 microM for SC.SS). The SC decoy-DNAs were found to be effective for regulating the DNA recognizing proteins.
