We show that fluorescent nanodiamonds (FNDs) are among the few types of nanosensors that enable direct optical reading of noncovalent molecular events. The unique sensing mechanism is based on switching between the negatively charged and neutral states of NV centers which is induced by the interaction of the FND surface with charged molecules.
- Publikační typ
- abstrakt z konference MeSH
Liposomes represent a biocompatible platform for the construction of self-assembling proteoliposomes using nickel or zinc metallochelation. Potential applications of such structures consist in the development of new biocompatible vaccination nanoparticles and drug delivery nanoparticle systems. Here, we describe the design and construction of a flow-through ultrafiltration cell suitable for the preparation of monodisperse liposomes enabled for metallochelation and, hence, the formation of proteoliposomes. The linkage of the cell with a fast protein liquid chromatography system facilitates automation of the procedure, which fits the criteria for upscaling. Proof-of-concept experiments are performed using a mixture of egg phosphatidyl choline and nickel-chelating lipid DOGS-NTA-Ni (1,2-dioleoyl-sn-glycero-3-{[N(5-amino-1-carboxypentyl)iminodiacetic acid]succinyl}(nickel salt)) to formulate proteoliposomes with proteins attached by metallochelation, including histidine (His)-tagged recombinant green fluorescent protein and rgp120 (derived from HIV-1 Env). These model proteoliposomes are characterized by gel permeation chromatography and by dynamic light scattering. Transmission electron microscopy and immunogold staining are used to characterize surface-bound proteins, revealing the tendency of rgp120 to form microdomains on liposome surfaces. These microdomains possess a two-dimensional crystal-like structure that is seen more precisely by atomic force microscopy.
- MeSH
- chelátory chemie MeSH
- histidin chemie genetika metabolismus MeSH
- HIV obalový protein gp120 chemie genetika metabolismus MeSH
- HIV-1 metabolismus MeSH
- imobilizované proteiny chemie genetika metabolismus MeSH
- lidé MeSH
- liposomy chemie MeSH
- micely MeSH
- mikroskopie atomárních sil MeSH
- nikl chemie MeSH
- oligopeptidy chemie genetika metabolismus MeSH
- proteolipidy chemie MeSH
- transmisní elektronová mikroskopie MeSH
- ultrafiltrace metody MeSH
- zelené fluorescenční proteiny chemie genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: A plausible strategy to reduce tumor progress is the inhibition of angiogenesis. Therefore, agents that efficiently suppress angiogenesis can be used for tumor suppression. We tested the antiangiogenic potential of a mitochondrially targeted analog of α-tocopheryl succinate (MitoVES), a compound with high propensity to induce apoptosis. RESULTS: MitoVES was found to efficiently kill proliferating endothelial cells (ECs) but not contact-arrested ECs or ECs deficient in mitochondrial DNA, and suppressed angiogenesis in vitro by inducing accumulation of reactive oxygen species and induction of apoptosis in proliferating/angiogenic ECs. Resistance of arrested ECs was ascribed, at least in part, to the lower mitochondrial inner transmembrane potential compared with the proliferating ECs, thus resulting in the lower level of mitochondrial uptake of MitoVES. Shorter-chain homologs of MitoVES were less efficient in angiogenesis inhibition, thus suggesting a molecular mechanism of its activity. Finally, MitoVES was found to suppress HER2-positive breast carcinomas in a transgenic mouse as well as inhibit tumor angiogenesis. The antiangiogenic efficacy of MitoVES was corroborated by its inhibitory activity on wound healing in vivo. INNOVATION AND CONCLUSION: We conclude that MitoVES, a mitochondrially targeted analog of α-tocopheryl succinate, is an efficient antiangiogenic agent of potential clinical relevance, exerting considerably higher activity than its untargeted counterpart. MitoVES may be helpful against cancer but may compromise wound healing.
- MeSH
- alfa-tokoferol analogy a deriváty farmakologie terapeutické užití MeSH
- apoptóza účinky léků MeSH
- buněčné linie MeSH
- endoteliální buňky účinky léků MeSH
- hojení ran účinky léků MeSH
- inhibitory angiogeneze chemie farmakologie terapeutické užití MeSH
- lidé MeSH
- mitochondriální DNA metabolismus MeSH
- mitochondrie účinky léků MeSH
- modely nemocí na zvířatech MeSH
- myši transgenní MeSH
- myši MeSH
- nádory krevní zásobení farmakoterapie MeSH
- patologická angiogeneze farmakoterapie MeSH
- proliferace buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
On the basis of the highly branched ovomucoid-type undecasaccharide that had been shown previously to be an endogenous ligand for CD69 leukocyte receptor, a systematic investigation of smaller oligosaccharide mimetics was performed based on linear and branched N-acetyl-d-hexosamine homooligomers prepared synthetically using hitherto unexplored reaction schemes. The systematic structure-activity studies revealed the tetrasaccharide GlcNAcbeta1-3(GlcNAcbeta1-4)(GlcNAcbeta1-6)GlcNAc (compound 52) and its alpha-benzyl derivative 49 as the best ligand for CD69 with IC(50) as high as 10(-9) M. This compound thus approaches the affinity of the classical high-affinity neoglycoprotein ligand GlcNAc(23)BSA. Compound 68, GlcNAc tetrasaccharide 52 dimerized through a hydrophilic flexible linker, turned out to be effective in activating CD69(+) lymphocytes. It also proved efficient in enhancing natural killing in vitro, decreasing the growth of tumors in vivo, and activating the CD69(+) tumor infiltrating lymphocytes examined ex vivo. This compound is thus a candidate for carbohydrate-based immunomodulators with promising antitumor potential.
- MeSH
- acetylglukosamin analogy a deriváty chemická syntéza chemie farmakologie MeSH
- aktivace lymfocytů MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- buňky NK účinky léků imunologie metabolismus MeSH
- CD antigeny metabolismus MeSH
- diferenciační antigeny T-lymfocytů metabolismus MeSH
- dimerizace MeSH
- imunologické faktory chemická syntéza chemie farmakologie MeSH
- krysa rodu rattus MeSH
- lektinové receptory NK-buněk - podrodina B metabolismus MeSH
- lektiny typu C metabolismus MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- ligandy MeSH
- melanom experimentální imunologie patologie MeSH
- molekulární mimikry MeSH
- molekulární modely MeSH
- molekulární sekvence - údaje MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- oligosacharidy chemická syntéza chemie farmakologie MeSH
- rekombinantní proteiny chemie MeSH
- sacharidové sekvence MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- publikace stažené z tisku MeSH
- techniky in vitro MeSH
- MeSH
- alfa-glukosidasy diagnostické užití MeSH
- beta-galaktosidasa diagnostické užití MeSH
- chromatografie afinitní * metody využití MeSH
- elektroforéza v polyakrylamidovém gelu metody využití MeSH
- glukoamylasa diagnostické užití MeSH
- glykosidhydrolasy * izolace a purifikace metabolismus MeSH
- krysa rodu rattus MeSH
- laktasa diagnostické užití MeSH
- sefarosa diagnostické užití izolace a purifikace MeSH
- statistika jako téma MeSH
- střevní sliznice enzymologie MeSH
- tenké střevo * enzymologie metabolismus MeSH
- thioglukosidy diagnostické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
