ABSTRACT
Platinum-resistant cancer cells are sensitive to changes in the levels of reactive oxidative species (ROS). Herein, we design a biotin-modified Ru(ii) complex as a photosensitizer (denoted as Ru-Biotin). Ru-Biotin can selectively target cancer cells and produce vast amounts of singlet oxygen under two-photon excitation at 820 nm leading to cell apoptosis. Ru-Biotin is therefore an excellent candidate to overcome platinum resistance via two-photon photodynamic therapy.
Subject(s)
Antineoplastic Agents/pharmacology , Biotin/analogs & derivatives , Biotin/pharmacology , Coordination Complexes/pharmacology , Photosensitizing Agents/pharmacology , Ruthenium/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Apoptosis/drug effects , Biotin/chemical synthesis , Biotin/radiation effects , Caspase 3/metabolism , Caspase 7/metabolism , Cell Line, Tumor , Coordination Complexes/chemical synthesis , Coordination Complexes/chemistry , Coordination Complexes/radiation effects , Humans , Infrared Rays , Photochemotherapy/methods , Photons , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Photosensitizing Agents/radiation effects , Singlet Oxygen/metabolismABSTRACT
Zinc(II) phthalocyanine containing [2-(tert-butoxycarbonyl)amino]ethoxy and iodine groups (A and B), as well as their deprotected mono-amino and tri-iodine zinc(II) phthalocyanine (2) were obtained. This structure surrounds by substituents with functional groups. From this perspective it can be used a starting material for many reactions and applications, such as sonogashira coupling, carbodiimide coupling. An example of a first diversification reaction of this compound was obtained with conjugation of a biotin. Asymmetrically biotin conjugated and heavy atom bearing zinc(II) phthalocyanine (3) were synthesized characterized for the first time and photophysical, photochemical and photobiological properties of these phthalocyanines were compared in this study.
Subject(s)
Biotin/analogs & derivatives , Biotin/chemistry , Coordination Complexes/chemistry , Indoles/chemistry , Photosensitizing Agents/chemistry , Zinc/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/radiation effects , Biotin/chemical synthesis , Biotin/radiation effects , Coordination Complexes/chemical synthesis , Coordination Complexes/radiation effects , Drug Stability , HeLa Cells , Humans , Indoles/chemical synthesis , Indoles/radiation effects , Photochemotherapy , Photolysis , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/radiation effects , Quantum Theory , Solubility , Ultraviolet Rays , Zinc/radiation effectsABSTRACT
Recently we reported that the transfection of cells by PEGylated lipoplexes becomes significantly better by binding the PEGylated lipoplexes to the surface of microbubbles and applying ultrasound. To further optimize this gene delivery system it is important to understand the working mechanism. This paper elucidates the cellular entry path of these lipoplexes. The results clearly show that the PEGylated lipoplexes, released from the microbubbles upon applying ultrasound, are not taken up by endocytosis, the most common route for nanoparticles to enter cells. Our data demonstrate that, upon implosion of the microbubbles, the PEGylated lipoplexes are released and are most probably able to passively diffuse through the cell membrane pores or become injected in the cytoplasm of the target cells. This is attractive as the in vivo use of PEGylated nanoparticles remains currently limited due to a decreased cellular uptake and inefficient escape of the PEGylated nanoparticles from the endosomes.
Subject(s)
Biotin/chemistry , Cytoplasm/metabolism , Liposomes/metabolism , Microbubbles , Phosphatidylethanolamines/chemistry , Polyethylene Glycols/chemistry , Sonication/methods , Biotin/radiation effects , Cell Membrane , Cell Survival/radiation effects , Endocytosis , Endosomes , Humans , Luciferases/metabolism , Melanoma/pathology , Phosphatidylethanolamines/radiation effects , Polyethylene Glycols/radiation effects , Transfection , Tumor Cells, CulturedABSTRACT
A novel strategy for enhanced molecular recognition that utilized standard complexation strategies in combination with light-induced, or photo-, polymerization was recently demonstrated. Creative and rational materials design aided in the development of macroinitiators that produce a specific binding event, which is then amplified through photo-initation and chain polymerization. This polymerization-based amplification system produced a positive result that was visibly recognizable with amounts as low as 1000 molecules.
Subject(s)
Biotechnology/methods , Molecular Diagnostic Techniques , Polymers/radiation effects , Ultraviolet Rays , Avidin/chemistry , Avidin/radiation effects , Biotin/chemistry , Biotin/radiation effects , Polymers/chemistry , Sensitivity and SpecificityABSTRACT
Based on the enzymatic saccharification of the various pulps in the previous 0.8 l ultrasonic stirred tank reactor, the ultrasound-enhanced saccharification of waste papers such as newspaper, carton paper, office paper etc. was carried out in the same reactor as well as larger scale stirred tank reactors of size 3.2 and 6.4 l. The saccharification of each waste paper was less enhanced in the larger reactor at a given ultrasonic intensity. This could be attributed to the decrease in the ultrasonic intensity per reaction volume, i.e., the specific ultrasonic intensity. Most waste papers were more efficiently hydrolyzed with increasing specific ultrasonic intensities, although newspaper was less efficiently done for a too high specific intensity. Such an adverse effect might be due to the fact that some impurities in the newspaper such as lignin were activated by an intensive ultrasonic irradiation to form a rigid and closed network, which inhibited the access and adsorption of cellulase on to the substrate surface. The previous kinetic model was found to be applicable to analyze and simulate the saccharification of each waste paper in the different ultrasonic reactors. The ultimate conversion of a substrate based on the total sugar concentration estimated for an infinite reaction time could be correlated as a function of the ratio of initial substrate to enzyme concentrations at a fixed specific ultrasonic intensity. Either the apparent rate constant or the ultimate conversion increased and tended to approach a constant with an increase in the specific ultrasonic intensity except for the case of newspaper, while neither the apparent Michaelis constant, product inhibition constant nor glucose formation equilibrium constant was influenced by the specific ultrasonic intensity.
Subject(s)
Avidin/chemistry , Avidin/radiation effects , Biotin/chemistry , Biotin/radiation effects , Mass Spectrometry , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Microspheres , Particle Size , Temperature , Thermogravimetry , UltrasonicsABSTRACT
While the strong biotin-avidin interaction has been widely used for the detection of biomolecules, its irreversibility complicates their isolation. We report the synthesis of a photocleavable biotin derivative (PCB) which eliminates many limitations of existing methods. This reagent contains a biotin moiety linked through a spacer arm to a photocleavable moiety, which reacts selectively with primary amino groups on any substrate. In experiments using [leucine]-enkephalin as a model substrate, we show that PCB retains its high affinity toward avidin/streptavidin and allows rapid (< 5 min) and efficient (> 99%) photorelease of the substrate in a completely unaltered form. Photocleavable biotins should be useful in numerous applications involving the isolation of proteins, nucleic acids, lipids, and cells.
Subject(s)
Biotin/analogs & derivatives , Biotin/radiation effects , Amino Acid Sequence , Biophysical Phenomena , Biophysics , Biotin/chemistry , Enkephalin, Leucine/chemistry , Indicators and Reagents , Molecular Sequence Data , Molecular Structure , PhotochemistryABSTRACT
Frozen solutions of biotinylated glucose-6-phosphate dehydrogenase and fluorescently tagged avidin were exposed to high energy ionizing radiation. Parallel experiments with peroxidase coupled to streptavidin and with biotinylated phycoerythrin were also performed. The loss of function of each compound was analyzed according to target theory. Target analysis revealed that the radiation-sensitive mass associated with the enzymatic activity and that associated with the fluorescence were unchanged by irradiation in the strongly coupled state. Therefore the noncovalent bonds between biotin and avidin do not permit the transfer of radiation-deposited energy in amounts sufficient to destroy the activity of apposing molecule.
