Наночастицы металлов. Опыт и перспективы применения в фармакологии и в клеточных биотехнологиях

1. Наночастицы металлов. Опыт и перспективы применения в фармакологии и в клеточных биотехнологиях.

2.

3. “VIOLATION” OVER THE FUNDAMENTAL PHYSICAL LAWS IN “NANOWORLD”

① Ohm Law doesn’t work.
② Superconductivity at mild conditions: Carbon Nanotubes.
③Superparamagnetism in MeO nanoclusters: q=f(Ø)…Fe2O3, MoO,…
④Metal melting point “nanoshift”: Ag, Au, Pt, Pd, Ir,…
⑤ Hormesis: Me/MeO nanosize-dependent paradoxical effects on enzyme
activity.

4. Limerick Glossary on Nanopharmacology

“MEDICINAL NANOPARTICLES”
Mandatory Criteria:
① 1.0 – 100 nm size range.
②R = f(E), size matters
barrier
permeability
target
affinity
pharmacokinetics
T1/2 = f(Ø)
③Zero or low metabolic rate.
④”Smart behavior”.
Effect reversibility/ homeostasis dependence.
⑤ Cluster – surface diffusion effects*.

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11. Ag-NPs: PHARMACOKINETICS RELATED ADVANTAGES FOR Biologically Active Peptides (BAP)

●T1/2/T0 Modulation.
●BBB Permeability to Increase.
●Spectrofluorimetric tracing (no IFP – NMR needed).
●Analgetic efects
Behavioral effects
remain
merely
intact
CAF effects
●BAP primary structure doesn’t make any difference.

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14. Waugh-Rattenau rule

Se2+ - Erythrocyte Glutathione Reductase
D
I
Mo2+
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/mL

15. Waugh-Rattenau rule

D
I
Cd2+
Cu/Zn-SOD
1
0,5
0
0
200
-0,5
-1
-1,5
Cd-NP
30-40 nm
Cd-NP
10nm
400
600
[Me], pg/mL

16. The Delbreaux-Brachet Rule

key regularity integral chart
BBB: Pp/Pa
T1/2/T*1/2
3n-5n
5n-7n
5n-7n
3n-5n
10
20
30
40
Ag-NP size, nm
50
60

17. Ukena – Thiele Effects

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
MeO
10
polar media
non-polar media
20 30 40
NP size, nm
50

18. TUMOR-SPECIFIC CYTOSTATIC EFFECT: Au-NPs

HCC
HALL
10
20
30
Au-NP size, nm
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

19.

20. BBB Permeability

BN-cytosol NP, pg/mg DNA
60
40
Se
20
Ag
Au
0
0
10
20
30
NP size, nm
(10mg/kg, i.v., 1hr, rat)
40

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22.

-[Co]PMC16
- Co2+
- polysomes
- crista
- RcPMC16

23.

Malignant B-cells treated with [Co2+]4PMC16
Purification control.
SDS-PAGE.
Mr≤5.0 kDa, WSP
GELFILTRATION.
Sephadex G25
Ion-exchange
Chromotography.
MonoQ.
Hydrophobic
Chromotography.
Phenyl-Sepharose.
Sequencing control
Cytosol
ULTRAFILTRATION.
Diaflo Y5.0 membranes

24. CAF[Co]PMC16 Nanobiotechnology for the HALL Patients Autohematotherapy

НALL patient
reinjection
Venous Blood
COLLECTION
Lymphocyte
total pool
CAF
lyophylization
crystallyzation
Pure
CAF
CAF isolation/purification:
Diaflo Y5.0/Sephadex G25/
MonoQ/Phenyl-Sepharose
[Co]PMC16
In Vitro
cultivation
Cell
lysate
Co2+
removal
SDS-PAGE
LC-MS
UV-Vis
SEQUENCING

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1.
Asp – Glu – Val – Phe – Trp – Phe – Asp
2.
Asp – Glu – Val – Trp – 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 – 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

26.

Known Co2+-promoted AT effect.
Assymmetrical compartmentization of protein synthesis
machinery in mitochondria.
Pure Co2+/Co-free PMC16 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 Co2+ -directed AT effect studies: does CAF could be
induced by another type of AT promoters?