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Медицинские нанотехнологии вводная лекция.ppt
- Количество слайдов: 27
Введение в нанотехнологии. Роль в биологии и медицине.
① Ohm Law doesn’t work. ② Superconductivity at mild conditions: Carbon Nanotubes. ③Superparamagnetism in Me. O nanoclusters: q=f(Ø)…Fe 2 O 3, Mo. O, … ④Metal melting point “nanoshift”: Ag, Au, Pt, Pd, Ir, … ⑤ Hormesis: Me/Me. O nanosize-dependent paradoxical effects on enzyme activity.
“MEDICINAL NANOPARTICLES” Mandatory Criteria: ① 1. 0 – 100 nm size range. ②R = f(E), size matters barrier permeability target affinity pharmacokinetics T 1/2 = f(Ø) ③Zero or low metabolic rate. ④”Smart behavior”. Effect reversibility/ homeostasis dependence. ⑤ Cluster – surface diffusion effects*.
●T 1/2/T 0 Modulation. ●BBB Permeability to Increase. ●Spectrofluorimetric tracing (no IFP – NMR needed). ●Analgetic efects Behavioral effects CAF effects remain merely intact ●BAP primary structure doesn’t make any difference.
Se 2+ - Erythrocyte Glutathione Reductase D I Mo 2+ 1 0. 5 0 0 200 -0. 5 -1 -1. 5 Mo-NP 50 -60 NP Mo-NP 10 -20 nm 400 600 [Me], pg/m. L
D I Cd 2+ Cu/Zn-SOD 1 0. 5 0 0 200 -0. 5 -1 -1. 5 Cd-NP 30 -40 nm Cd-NP 10 nm 400 600 [Me], pg/m. L
key regularity integral chart BBB: Pp/Pa T 1/2/T*1/2 3 n-5 n 5 n-7 n 3 n-5 n 10 20 30 40 Ag-NP size, nm 50 60
The “alloy-ion” border diffusion Cs, Cd, Co, Mo, Fe, Zn, Cr, Cu, Mn, Mg q Me(II) 10 20 30 40 NP size, nm 50 q Me. O 10 polar media non-polar media 20 30 40 NP size, nm 50
HCC HALL 10 20 Au-NP size, nm 30 1. 0 Rs 0. 5 10 [Au], pg/mg DNA 5 Rs 1. 0 [Au], pg/mg DNA 10 5 0. 5 10 20 Au-NP size, nm 30
BN-cytosol NP, pg/mg DNA 60 40 Se 20 Ag Au 0 0 10 20 30 NP size, nm (10 mg/kg, i. v. , 1 hr, rat) 40
-[Co]PMC 16 - Co 2+ - polysomes - crista - Rc. PMC 16
TECHNOLOGICAL CASCADE OF THE CAF ISOLATON/PUREFICATION Malignant B-cells treated with [Co 2+]4 PMC 16 SDS-PAGE. Purification control. Mr≤ 5. 0 k. Da, WSP GELFILTRATION. Sephadex G 25 Ion-exchange Chromotography. Mono. Q. Hydrophobic Chromotography. Phenyl-Sepharose. Sequencing control Cytosol ULTRAFILTRATION. Diaflo Y 5. 0 membranes
CAF[Co]PMC 16 Nanobiotechnology for the HALL Patients Autohematotherapy НALL patient reinjection Venous Blood COLLECTION Lymphocyte total pool CAF lyophylization crystallyzation Pure CAF isolation/purification: Diaflo Y 5. 0/Sephadex G 25/ Mono. Q/Phenyl-Sepharose [Co]PMC 16 In Vitro cultivation Cell lysate Co 2+ removal SDS-PAGE LC-MS UV-Vis SEQUENCING
CAF HOMOLOGY PATTERN 1. Asp – Glu – Val – Phe – Trp – Phe – Asp 2. Asp – Glu – Val – Trp – Phe – Asp 3. Asp – Glu – Val – Phe – Tyr – Phe – Asp 4. Asp – Glu – Leu – Phe – Trp – Phe – Asp 5. Asp – Glu – Leu – Phe – Trp – Phe – Asp 6. Asp – Glu – Val – Iso – Trp – Phe – Asp 7. Asp – Glu – Trp – Phe – Asp 8. Asp – Glu – Val – Tyr – Trp – Phe – Asp 9. Asp – Glu – Val – Trp – Iso – Phe – Asp 10. Asp – Glu – Sep – Phe – Trp – Phe – Asp 11. Asp – Glu – Val – Asp – Trp – Phe – Asp 12. Asp – Glu – Typ – Phe – Trp – Phe – Asp 13. Asp – Glu – Val – His – Trp – Phe – Asp 14. Asp – Glu – Leu – Phe – Trp – Phe – Asp 15. Asp – Glu – Trp – Phe – Ser – Phe – Asp 16. Asp – Glu – Val – Trp – Leu – Phe – Asp
KEY REASONS FOR A CONCLUSION ON THE MITOCHONDRIAL ABORTIVE TRANSLATION ORIGIN OF THE CAF Known Co 2+-promoted AT effect. Assymmetrical compartmentization of protein synthesis machinery in mitochondria. Pure Co 2+/Co-free PMC 16 effects on mitochondria translation in vitro. No CAF production in matured cells. ? Porphyrin-signalling domains in mitochondria membranes: rare abundance, non-random distribution (compartmentization). ? CAF-producing “pockets” in mitochondria. ? CAF/Mt-matrix proteins homology. ? Other than Co 2+ -directed AT effect studies: does CAF could be induced by another type of AT promoters?
Медицинские нанотехнологии вводная лекция.ppt