SlideShare a Scribd company logo
A NOVEL FAMILY OF MEDICINAL
        NANOPARTICLES TO PROMOTE THE
         MAGNETIC ISOTOPE EFFECT FOR
          PHARMACOLOGICAL PURPOSES

    Dmitry A. Kuznetsov
    Vladimir P. Chekhonin


N.N. Semenov Institute for Chemical Physics, Russian Academy of
Sciences, Moscow, Russia


Department of Medicinal Nanobiotechnology, N.I. Pirogov Russian State
Medical University, Moscow, Russia
THE CREATINE KINASE ACTIVE SITE NANOTOPOLOGY
The rate of ATP formation by mitochondria (A) and by creatine
        kinase (B) as a function of magnesium isotope
                      intact mitochondria

     mitochondria subjected to a selective blockade of oxidative
            phosphorylation by 1-methylnicotine amide.


    A                                        B




                                                    25



                                   1.0
                                             24           26




    The yield of ATP is given in mmole/g total protein
ION – RADICAL PAIRS
     FORMATION
(SINGLET – TRIPLET PATH
        SHIFT)
      MECHANISM
OF THE 25Mg MAGNETIC
   ISOTOPE EFFECT
      EXPRESSED
   IN A BIOLOGICAL
  PHOSPHORYLATION
      PRECESSES
        (Mt-CK)
THE CK CATALYTIC SITE NANOTOPOLOGY IMPACT ONTO
    THE REAGENTS ELECTRON DENSITY OVERLAP




    A combined systemic solution of both Schroedinger
           and Poissone equations processed
The GPK reaction ion-radical mechanism
A phosphorylation rate expressed as the yield (Y) of -[32P]ATP
produced by 1 mg of pure enzyme per 1 min related to the ATP synthesis
 rate (Y0) directed by enzyme sample with a natural abundance of Mg2+
         isotopes as a function of 25Mg content in CK active sites.
Buckminsterfullerene(C60)-2-(butadiene-1-yl)-
 -tetra(o--aminobutyryl-o-phtalyl)porphyrin
         PORPHYLLERENE – MC16

                        COO-                                        -OOC

                        CH2                                            CH2

                       HC      NH2
                                           2+ H N               2      CH

                       H2C      COO-
                                       2 Mg -OOC                       CH2


                                       COO-       -OOC




                                              N

                                       N      Fe         N

                                              N



                                       COO-       -OOC


                                COO-                         -OOC      CH2
                         CH2

                       HC      NH2                            H2N      CH
                                               2+
                         CH2               2 Mg                        CH2

                         COO-                                       -OOC
PMC16 CATIONITE PROPERTIES AND THE NANOCLUSTERS FORMATION AS A
                        FUNCTION OF pH

                                                            14.8nm


                                          10.2nm

                                          6.4nm
                                                   4.7nm
                                                           3.2nm
                                                           1.15nm




                                     pH

        Blue arrow shows the iron-dextrane sphere exclusion limit
      Blue arrow shows the iron-dextrane sphere exclusion limit


                             , portion of the total PMC16 magnesium
THE EFFECT OF A PMC16 – TARGETED DELIVERY OF Mg2+ ON
THE DOXORUBICIN (DXR) PRE – SUPPRESSED ATP
PRODUCTION IN RAT MYOCARDIUM




           0.8 DL50 DXR, i.v., 6 hrs → PMC16, i.v., 6 hrs
SYNERGISM OF THE MITOCHONDRIAL MATRIX CK ACTIVITY,
  MAGNESIUM CATIONS INFLUX AND THE FREE PROTONS
                  EXCESS DEGREE



 CK Relative Activity




                        The isolated rat myocardium mitochondria tested.
            Yellow / Red stands for the spinless / spin Mg isotopes ratio.
SYNERGISM OF THE ATP YIELD, OXYGEN CONSUMPTION AND
THE Mg2+ INFLUX IN THE PERFUSED ISOLATED RABBIT HEART
                     MUSCLE TISSUE


A                                     B




                                   ATP yield, Y/Yo
    ATP yield, Y/Yo




    A – Zero spin magnesium test   B – Magnetic magnesium test
ELECTRON TRANSMITTING MICROPHOTOGRAMS OF THE
         RAT MYOCARDIOCYTIC PERINUCLEAR AREAS




A                                  B




                                   D
C

       A, C – PMC16 related hypoxia preventing effect
       B – Inhalation oxygen deficiency hypoxia model
                  D – Intact myocardium
PMC16 CLUSTER POSITIONING INSIDE THE RAT
MYOCARDIOCYTIC MITOCHONDRIAL MEMBRANE IN METABOLIC
    ACIDOSIS (a, c) AND IN NORMAL CONDITIONS (b, d)




         a, b – Laser contrast (Nanofinder-S-6A) images
              C, d – Confocal scanning microscopy
PMC16 nanoclusters immobilized on acetyl cellulose membrane

a – LCM, pH 7.00
b – LCM, pH 8.40
c – AFM, pH 8.80
A HIGHLY SELECTIVE TRAGETING OF PMC16 NANOPARTICELS TOWARDS THE
RAT HEART MUSCLE IN A COURSE OF THE LONG – TERM ADMINISTRATION
OF AN EXTRA LOW DRUG DOSAGE
NOTE: DXR, 20 mg/kg/24 hrs, i.v.:
       MNA, 10 mg/kg/24 hrs, i.v.:
CONCLUSIONS
PORPHYRINE ADDUCTS OF FULLERENE C60,
A NEW FAMILY OF MEDICINAL NANOPARTICLES TO
MEET THE FOLLOWING EXPECTATIONS:
• Tissue-selective targeted delivery of 25Mg2+ paramagnetics
    to the porphyrin-signaling cell compartments in
    myocardium and, to a lesser degree, lymphocytes
•   The 25Mg2+-related magnetic isotope effect to promote a
    local and fast, jump-up increase of ATP production, even
    in the tissue oxygen deplete of any sort
•   Smart nanoparticles behavior while in Mt-membrane, i.e. a
    gradual 25Mg2+ release that occurs exclusively in response
    to the tissue hypoxia-caused metabolic acidosis
•   Low toxic, safe, efficient and completely eliminable (C60-
    clearing / porphyrin metabolizing) agents, all suitable for
    either short or long term administration schemes

More Related Content

What's hot

Photosynthesis
PhotosynthesisPhotosynthesis
Photosynthesis
Dayananda Salam
 
47 ch10calvincycle2008
47 ch10calvincycle200847 ch10calvincycle2008
47 ch10calvincycle2008sbarkanic
 
Week 9
Week 9Week 9
Week 9
kristenw3
 
Cell resp notes
Cell resp notesCell resp notes
Cell resp notes
farrellw
 
Photosynthesis cellular respiration poster project grading sheet
Photosynthesis cellular respiration poster project grading sheetPhotosynthesis cellular respiration poster project grading sheet
Photosynthesis cellular respiration poster project grading sheetMaria Donohue
 
Photosynthesis
PhotosynthesisPhotosynthesis
Photosynthesis
Raja Ariska
 
Photosynthesis 6 light independent reaction
Photosynthesis 6 light independent reactionPhotosynthesis 6 light independent reaction
Photosynthesis 6 light independent reactionstvb2170
 
Dark Reaction Phase
Dark Reaction PhaseDark Reaction Phase
Dark Reaction Phase
anikaisthename
 
Powerpoint Metabolisme 2
Powerpoint  Metabolisme 2Powerpoint  Metabolisme 2
Powerpoint Metabolisme 2
Dhita Ayu Distarasiswa
 
Nucleotide chemistry and metabolism with ece
Nucleotide chemistry and metabolism with eceNucleotide chemistry and metabolism with ece
Nucleotide chemistry and metabolism with ece
Prof Viyatprajna Acharya
 
Respiration
RespirationRespiration
Respiration
yentruocfarrow
 
Cellular respiration
Cellular respirationCellular respiration
Cellular respiration
Eman Vidallo
 
Amino acid Analyzer
Amino acid AnalyzerAmino acid Analyzer
Amino acid Analyzer
Unaiza Chaudhary
 
Photosynthesis ruchi (4)
Photosynthesis ruchi (4)Photosynthesis ruchi (4)
Photosynthesis ruchi (4)
Ruchi Choudhary
 
Photosynthesis dark reaction
Photosynthesis dark reaction Photosynthesis dark reaction
Photosynthesis dark reaction
varshaYadav102
 
Photosynthesis 6 light independent reaction
Photosynthesis 6 light independent reactionPhotosynthesis 6 light independent reaction
Photosynthesis 6 light independent reactionstvb2170
 
KIMOR 2 : asam karboksilat
KIMOR 2 : asam karboksilatKIMOR 2 : asam karboksilat
KIMOR 2 : asam karboksilat
university of muhammadiyah malang
 

What's hot (20)

Photosynthesis
PhotosynthesisPhotosynthesis
Photosynthesis
 
47 ch10calvincycle2008
47 ch10calvincycle200847 ch10calvincycle2008
47 ch10calvincycle2008
 
Wolf rearrangement
Wolf rearrangementWolf rearrangement
Wolf rearrangement
 
Week 9
Week 9Week 9
Week 9
 
Cell resp notes
Cell resp notesCell resp notes
Cell resp notes
 
Photosynthesis cellular respiration poster project grading sheet
Photosynthesis cellular respiration poster project grading sheetPhotosynthesis cellular respiration poster project grading sheet
Photosynthesis cellular respiration poster project grading sheet
 
Photosynthesis
PhotosynthesisPhotosynthesis
Photosynthesis
 
Photosynthesis 6 light independent reaction
Photosynthesis 6 light independent reactionPhotosynthesis 6 light independent reaction
Photosynthesis 6 light independent reaction
 
Dark Reaction Phase
Dark Reaction PhaseDark Reaction Phase
Dark Reaction Phase
 
Powerpoint Metabolisme 2
Powerpoint  Metabolisme 2Powerpoint  Metabolisme 2
Powerpoint Metabolisme 2
 
Nucleotide chemistry and metabolism with ece
Nucleotide chemistry and metabolism with eceNucleotide chemistry and metabolism with ece
Nucleotide chemistry and metabolism with ece
 
Respiration
RespirationRespiration
Respiration
 
Cellular respiration
Cellular respirationCellular respiration
Cellular respiration
 
Amino acid Analyzer
Amino acid AnalyzerAmino acid Analyzer
Amino acid Analyzer
 
Photosynthesis ruchi (4)
Photosynthesis ruchi (4)Photosynthesis ruchi (4)
Photosynthesis ruchi (4)
 
Photosynthesis dark reaction
Photosynthesis dark reaction Photosynthesis dark reaction
Photosynthesis dark reaction
 
Photosynthesis 6 light independent reaction
Photosynthesis 6 light independent reactionPhotosynthesis 6 light independent reaction
Photosynthesis 6 light independent reaction
 
KIMOR 2 : asam karboksilat
KIMOR 2 : asam karboksilatKIMOR 2 : asam karboksilat
KIMOR 2 : asam karboksilat
 
Carbs
CarbsCarbs
Carbs
 
Glycolysis
GlycolysisGlycolysis
Glycolysis
 

Similar to Д.А.Кузнецев. Университет им.Н.И.Пирогова(РГМУ)

Research Paper Presentation by Ariful Islam
Research Paper Presentation by Ariful IslamResearch Paper Presentation by Ariful Islam
Research Paper Presentation by Ariful Islam
ArifulIslam665
 
Selective Cellobiose Photoreforming for Simultaneous Gluconic Acid and Syngas...
Selective Cellobiose Photoreforming for Simultaneous Gluconic Acid and Syngas...Selective Cellobiose Photoreforming for Simultaneous Gluconic Acid and Syngas...
Selective Cellobiose Photoreforming for Simultaneous Gluconic Acid and Syngas...
Pawan Kumar
 
Comparison of the structures and vibrational modes of carboxybiotin and n car...
Comparison of the structures and vibrational modes of carboxybiotin and n car...Comparison of the structures and vibrational modes of carboxybiotin and n car...
Comparison of the structures and vibrational modes of carboxybiotin and n car...
John Clarkson
 
Pawan chem eur j graphene phthalocyanine
Pawan chem eur j graphene phthalocyaninePawan chem eur j graphene phthalocyanine
Pawan chem eur j graphene phthalocyanine
Pawan Kumar
 
intro_to_enzymes.ppt
intro_to_enzymes.pptintro_to_enzymes.ppt
intro_to_enzymes.ppt
AbshiroBeyene2
 
Hari talk sdmc_puri_final
Hari talk sdmc_puri_finalHari talk sdmc_puri_final
Hari talk sdmc_puri_final
Nitish Pal
 
PHA(Eng)
PHA(Eng)PHA(Eng)
PHA(Eng)
GiuseppePuzzo
 
Induction of Luminol Chemiluminescence by the Manganese Cluster of the Photos...
Induction of Luminol Chemiluminescence by the Manganese Cluster of the Photos...Induction of Luminol Chemiluminescence by the Manganese Cluster of the Photos...
Induction of Luminol Chemiluminescence by the Manganese Cluster of the Photos...Igor Putrenko
 
Pawan CO2 REDUCTION PPT
Pawan CO2 REDUCTION PPTPawan CO2 REDUCTION PPT
Pawan CO2 REDUCTION PPT
Pawan Kumar
 
Pawan rsc advance tin phthalocyanine
Pawan rsc advance tin phthalocyaninePawan rsc advance tin phthalocyanine
Pawan rsc advance tin phthalocyanine
Pawan Kumar
 
Construction Of Near Infrared Chiroptical Switches Based On Electrochromic Vi...
Construction Of Near Infrared Chiroptical Switches Based On Electrochromic Vi...Construction Of Near Infrared Chiroptical Switches Based On Electrochromic Vi...
Construction Of Near Infrared Chiroptical Switches Based On Electrochromic Vi...
niba50
 
Characterization of biodegradable poly(3 hydroxybutyrate-co-butyleneadipate) ...
Characterization of biodegradable poly(3 hydroxybutyrate-co-butyleneadipate) ...Characterization of biodegradable poly(3 hydroxybutyrate-co-butyleneadipate) ...
Characterization of biodegradable poly(3 hydroxybutyrate-co-butyleneadipate) ...
Giuseppe Puzzo
 
Theoretical calculations of chemical shifts of metal (Hg (II), Pb (II), Ag (I...
Theoretical calculations of chemical shifts of metal (Hg (II), Pb (II), Ag (I...Theoretical calculations of chemical shifts of metal (Hg (II), Pb (II), Ag (I...
Theoretical calculations of chemical shifts of metal (Hg (II), Pb (II), Ag (I...
iosrphr_editor
 
Research proposal.pptx
Research proposal.pptxResearch proposal.pptx
Research proposal.pptx
Rajeev Chand Nishad
 
Andrey rubin target photosynthetic products and chlorophyll fluorescence
Andrey rubin target photosynthetic products and chlorophyll fluorescenceAndrey rubin target photosynthetic products and chlorophyll fluorescence
Andrey rubin target photosynthetic products and chlorophyll fluorescenceigorod
 
Application Note: Determination of Impurities in Silica Wafers with the NexIO...
Application Note: Determination of Impurities in Silica Wafers with the NexIO...Application Note: Determination of Impurities in Silica Wafers with the NexIO...
Application Note: Determination of Impurities in Silica Wafers with the NexIO...
PerkinElmer, Inc.
 
Electrochemical properties of myoglobin deposited on multi walled carbon nano...
Electrochemical properties of myoglobin deposited on multi walled carbon nano...Electrochemical properties of myoglobin deposited on multi walled carbon nano...
Electrochemical properties of myoglobin deposited on multi walled carbon nano...
Expand_Lives
 

Similar to Д.А.Кузнецев. Университет им.Н.И.Пирогова(РГМУ) (20)

Research Paper Presentation by Ariful Islam
Research Paper Presentation by Ariful IslamResearch Paper Presentation by Ariful Islam
Research Paper Presentation by Ariful Islam
 
Selective Cellobiose Photoreforming for Simultaneous Gluconic Acid and Syngas...
Selective Cellobiose Photoreforming for Simultaneous Gluconic Acid and Syngas...Selective Cellobiose Photoreforming for Simultaneous Gluconic Acid and Syngas...
Selective Cellobiose Photoreforming for Simultaneous Gluconic Acid and Syngas...
 
Comparison of the structures and vibrational modes of carboxybiotin and n car...
Comparison of the structures and vibrational modes of carboxybiotin and n car...Comparison of the structures and vibrational modes of carboxybiotin and n car...
Comparison of the structures and vibrational modes of carboxybiotin and n car...
 
Pawan chem eur j graphene phthalocyanine
Pawan chem eur j graphene phthalocyaninePawan chem eur j graphene phthalocyanine
Pawan chem eur j graphene phthalocyanine
 
intro_to_enzymes.ppt
intro_to_enzymes.pptintro_to_enzymes.ppt
intro_to_enzymes.ppt
 
Hari talk sdmc_puri_final
Hari talk sdmc_puri_finalHari talk sdmc_puri_final
Hari talk sdmc_puri_final
 
PHA(Eng)
PHA(Eng)PHA(Eng)
PHA(Eng)
 
Induction of Luminol Chemiluminescence by the Manganese Cluster of the Photos...
Induction of Luminol Chemiluminescence by the Manganese Cluster of the Photos...Induction of Luminol Chemiluminescence by the Manganese Cluster of the Photos...
Induction of Luminol Chemiluminescence by the Manganese Cluster of the Photos...
 
Pawan CO2 REDUCTION PPT
Pawan CO2 REDUCTION PPTPawan CO2 REDUCTION PPT
Pawan CO2 REDUCTION PPT
 
Pawan rsc advance tin phthalocyanine
Pawan rsc advance tin phthalocyaninePawan rsc advance tin phthalocyanine
Pawan rsc advance tin phthalocyanine
 
Construction Of Near Infrared Chiroptical Switches Based On Electrochromic Vi...
Construction Of Near Infrared Chiroptical Switches Based On Electrochromic Vi...Construction Of Near Infrared Chiroptical Switches Based On Electrochromic Vi...
Construction Of Near Infrared Chiroptical Switches Based On Electrochromic Vi...
 
Characterization of biodegradable poly(3 hydroxybutyrate-co-butyleneadipate) ...
Characterization of biodegradable poly(3 hydroxybutyrate-co-butyleneadipate) ...Characterization of biodegradable poly(3 hydroxybutyrate-co-butyleneadipate) ...
Characterization of biodegradable poly(3 hydroxybutyrate-co-butyleneadipate) ...
 
Theoretical calculations of chemical shifts of metal (Hg (II), Pb (II), Ag (I...
Theoretical calculations of chemical shifts of metal (Hg (II), Pb (II), Ag (I...Theoretical calculations of chemical shifts of metal (Hg (II), Pb (II), Ag (I...
Theoretical calculations of chemical shifts of metal (Hg (II), Pb (II), Ag (I...
 
A05620107
A05620107A05620107
A05620107
 
NMR
NMRNMR
NMR
 
PHA(eng)
PHA(eng)PHA(eng)
PHA(eng)
 
Research proposal.pptx
Research proposal.pptxResearch proposal.pptx
Research proposal.pptx
 
Andrey rubin target photosynthetic products and chlorophyll fluorescence
Andrey rubin target photosynthetic products and chlorophyll fluorescenceAndrey rubin target photosynthetic products and chlorophyll fluorescence
Andrey rubin target photosynthetic products and chlorophyll fluorescence
 
Application Note: Determination of Impurities in Silica Wafers with the NexIO...
Application Note: Determination of Impurities in Silica Wafers with the NexIO...Application Note: Determination of Impurities in Silica Wafers with the NexIO...
Application Note: Determination of Impurities in Silica Wafers with the NexIO...
 
Electrochemical properties of myoglobin deposited on multi walled carbon nano...
Electrochemical properties of myoglobin deposited on multi walled carbon nano...Electrochemical properties of myoglobin deposited on multi walled carbon nano...
Electrochemical properties of myoglobin deposited on multi walled carbon nano...
 

More from Pharmcluster

К.К.Зайцев, МФТИ
К.К.Зайцев, МФТИК.К.Зайцев, МФТИ
К.К.Зайцев, МФТИPharmcluster
 
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова Pharmcluster
 
зайцев новый корпус бфкс9
зайцев новый корпус бфкс9зайцев новый корпус бфкс9
зайцев новый корпус бфкс9Pharmcluster
 
А.Улитин, ООО "Мепротек"
А.Улитин, ООО "Мепротек" А.Улитин, ООО "Мепротек"
А.Улитин, ООО "Мепротек" Pharmcluster
 
А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC Pharmcluster
 
И.Тетерин, Gurus Capital
И.Тетерин, Gurus Capital И.Тетерин, Gurus Capital
И.Тетерин, Gurus Capital Pharmcluster
 
П.Федичев, Квантум фармасьютикал
П.Федичев, Квантум фармасьютикал П.Федичев, Квантум фармасьютикал
П.Федичев, Квантум фармасьютикал Pharmcluster
 
К.К.Зайцев, МФТИ
К.К.Зайцев, МФТИК.К.Зайцев, МФТИ
К.К.Зайцев, МФТИPharmcluster
 
А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC Pharmcluster
 
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.ОвчинниковаА.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.ОвчинниковаPharmcluster
 
К.К.Зайцев, БФК"Северный"
К.К.Зайцев, БФК"Северный"К.К.Зайцев, БФК"Северный"
К.К.Зайцев, БФК"Северный"Pharmcluster
 
К.К.Зайцев, БФК"Северный"
К.К.Зайцев, БФК"Северный"К.К.Зайцев, БФК"Северный"
К.К.Зайцев, БФК"Северный"Pharmcluster
 
А.А.Сеид-Гусейнов, "Искусственные органы"АМТН
А.А.Сеид-Гусейнов, "Искусственные органы"АМТНА.А.Сеид-Гусейнов, "Искусственные органы"АМТН
А.А.Сеид-Гусейнов, "Искусственные органы"АМТНPharmcluster
 
мжельский Investment & rating for chemrar 13 may 2011 v1
мжельский Investment & rating for chemrar 13 may 2011 v1мжельский Investment & rating for chemrar 13 may 2011 v1
мжельский Investment & rating for chemrar 13 may 2011 v1Pharmcluster
 
А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC Pharmcluster
 
А.Улитин, ООО "Мепротек"
А.Улитин, ООО "Мепротек"А.Улитин, ООО "Мепротек"
А.Улитин, ООО "Мепротек"Pharmcluster
 
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.ОвчинниковаА.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.ОвчинниковаPharmcluster
 
И.Тетерин, Gurus Capital
И.Тетерин,  Gurus CapitalИ.Тетерин,  Gurus Capital
И.Тетерин, Gurus CapitalPharmcluster
 
П.Федичев, Квантум фармасьютикал
П.Федичев, Квантум фармасьютикал П.Федичев, Квантум фармасьютикал
П.Федичев, Квантум фармасьютикал Pharmcluster
 

More from Pharmcluster (20)

К.К.Зайцев, МФТИ
К.К.Зайцев, МФТИК.К.Зайцев, МФТИ
К.К.Зайцев, МФТИ
 
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
 
зайцев новый корпус бфкс9
зайцев новый корпус бфкс9зайцев новый корпус бфкс9
зайцев новый корпус бфкс9
 
А.Улитин, ООО "Мепротек"
А.Улитин, ООО "Мепротек" А.Улитин, ООО "Мепротек"
А.Улитин, ООО "Мепротек"
 
А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC
 
И.Тетерин, Gurus Capital
И.Тетерин, Gurus Capital И.Тетерин, Gurus Capital
И.Тетерин, Gurus Capital
 
П.Федичев, Квантум фармасьютикал
П.Федичев, Квантум фармасьютикал П.Федичев, Квантум фармасьютикал
П.Федичев, Квантум фармасьютикал
 
кузнецов
кузнецовкузнецов
кузнецов
 
К.К.Зайцев, МФТИ
К.К.Зайцев, МФТИК.К.Зайцев, МФТИ
К.К.Зайцев, МФТИ
 
А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC
 
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.ОвчинниковаА.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
 
К.К.Зайцев, БФК"Северный"
К.К.Зайцев, БФК"Северный"К.К.Зайцев, БФК"Северный"
К.К.Зайцев, БФК"Северный"
 
К.К.Зайцев, БФК"Северный"
К.К.Зайцев, БФК"Северный"К.К.Зайцев, БФК"Северный"
К.К.Зайцев, БФК"Северный"
 
А.А.Сеид-Гусейнов, "Искусственные органы"АМТН
А.А.Сеид-Гусейнов, "Искусственные органы"АМТНА.А.Сеид-Гусейнов, "Искусственные органы"АМТН
А.А.Сеид-Гусейнов, "Искусственные органы"АМТН
 
мжельский Investment & rating for chemrar 13 may 2011 v1
мжельский Investment & rating for chemrar 13 may 2011 v1мжельский Investment & rating for chemrar 13 may 2011 v1
мжельский Investment & rating for chemrar 13 may 2011 v1
 
А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC А.А.Мжельский, Reed Elsever LLC
А.А.Мжельский, Reed Elsever LLC
 
А.Улитин, ООО "Мепротек"
А.Улитин, ООО "Мепротек"А.Улитин, ООО "Мепротек"
А.Улитин, ООО "Мепротек"
 
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.ОвчинниковаА.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
А.Н.Мурашев, ИБХ РАН им.академиков М.М.Шемякина и Ю.А.Овчинникова
 
И.Тетерин, Gurus Capital
И.Тетерин,  Gurus CapitalИ.Тетерин,  Gurus Capital
И.Тетерин, Gurus Capital
 
П.Федичев, Квантум фармасьютикал
П.Федичев, Квантум фармасьютикал П.Федичев, Квантум фармасьютикал
П.Федичев, Квантум фармасьютикал
 

Д.А.Кузнецев. Университет им.Н.И.Пирогова(РГМУ)

  • 1. A NOVEL FAMILY OF MEDICINAL NANOPARTICLES TO PROMOTE THE MAGNETIC ISOTOPE EFFECT FOR PHARMACOLOGICAL PURPOSES Dmitry A. Kuznetsov Vladimir P. Chekhonin N.N. Semenov Institute for Chemical Physics, Russian Academy of Sciences, Moscow, Russia Department of Medicinal Nanobiotechnology, N.I. Pirogov Russian State Medical University, Moscow, Russia
  • 2. THE CREATINE KINASE ACTIVE SITE NANOTOPOLOGY
  • 3.
  • 4. The rate of ATP formation by mitochondria (A) and by creatine kinase (B) as a function of magnesium isotope intact mitochondria mitochondria subjected to a selective blockade of oxidative phosphorylation by 1-methylnicotine amide. A B 25 1.0 24 26 The yield of ATP is given in mmole/g total protein
  • 5. ION – RADICAL PAIRS FORMATION (SINGLET – TRIPLET PATH SHIFT) MECHANISM OF THE 25Mg MAGNETIC ISOTOPE EFFECT EXPRESSED IN A BIOLOGICAL PHOSPHORYLATION PRECESSES (Mt-CK)
  • 6. THE CK CATALYTIC SITE NANOTOPOLOGY IMPACT ONTO THE REAGENTS ELECTRON DENSITY OVERLAP A combined systemic solution of both Schroedinger and Poissone equations processed
  • 7. The GPK reaction ion-radical mechanism
  • 8. A phosphorylation rate expressed as the yield (Y) of -[32P]ATP produced by 1 mg of pure enzyme per 1 min related to the ATP synthesis rate (Y0) directed by enzyme sample with a natural abundance of Mg2+ isotopes as a function of 25Mg content in CK active sites.
  • 9. Buckminsterfullerene(C60)-2-(butadiene-1-yl)- -tetra(o--aminobutyryl-o-phtalyl)porphyrin PORPHYLLERENE – MC16 COO- -OOC CH2 CH2 HC NH2 2+ H N 2 CH H2C COO- 2 Mg -OOC CH2 COO- -OOC N N Fe N N COO- -OOC COO- -OOC CH2 CH2 HC NH2 H2N CH 2+ CH2 2 Mg CH2 COO- -OOC
  • 10. PMC16 CATIONITE PROPERTIES AND THE NANOCLUSTERS FORMATION AS A FUNCTION OF pH 14.8nm 10.2nm 6.4nm 4.7nm 3.2nm 1.15nm pH Blue arrow shows the iron-dextrane sphere exclusion limit Blue arrow shows the iron-dextrane sphere exclusion limit , portion of the total PMC16 magnesium
  • 11. THE EFFECT OF A PMC16 – TARGETED DELIVERY OF Mg2+ ON THE DOXORUBICIN (DXR) PRE – SUPPRESSED ATP PRODUCTION IN RAT MYOCARDIUM 0.8 DL50 DXR, i.v., 6 hrs → PMC16, i.v., 6 hrs
  • 12. SYNERGISM OF THE MITOCHONDRIAL MATRIX CK ACTIVITY, MAGNESIUM CATIONS INFLUX AND THE FREE PROTONS EXCESS DEGREE CK Relative Activity The isolated rat myocardium mitochondria tested. Yellow / Red stands for the spinless / spin Mg isotopes ratio.
  • 13. SYNERGISM OF THE ATP YIELD, OXYGEN CONSUMPTION AND THE Mg2+ INFLUX IN THE PERFUSED ISOLATED RABBIT HEART MUSCLE TISSUE A B ATP yield, Y/Yo ATP yield, Y/Yo A – Zero spin magnesium test B – Magnetic magnesium test
  • 14.
  • 15.
  • 16.
  • 17.
  • 18.
  • 19. ELECTRON TRANSMITTING MICROPHOTOGRAMS OF THE RAT MYOCARDIOCYTIC PERINUCLEAR AREAS A B D C A, C – PMC16 related hypoxia preventing effect B – Inhalation oxygen deficiency hypoxia model D – Intact myocardium
  • 20. PMC16 CLUSTER POSITIONING INSIDE THE RAT MYOCARDIOCYTIC MITOCHONDRIAL MEMBRANE IN METABOLIC ACIDOSIS (a, c) AND IN NORMAL CONDITIONS (b, d) a, b – Laser contrast (Nanofinder-S-6A) images C, d – Confocal scanning microscopy
  • 21. PMC16 nanoclusters immobilized on acetyl cellulose membrane a – LCM, pH 7.00 b – LCM, pH 8.40 c – AFM, pH 8.80
  • 22. A HIGHLY SELECTIVE TRAGETING OF PMC16 NANOPARTICELS TOWARDS THE RAT HEART MUSCLE IN A COURSE OF THE LONG – TERM ADMINISTRATION OF AN EXTRA LOW DRUG DOSAGE
  • 23. NOTE: DXR, 20 mg/kg/24 hrs, i.v.: MNA, 10 mg/kg/24 hrs, i.v.:
  • 24.
  • 25.
  • 26. CONCLUSIONS PORPHYRINE ADDUCTS OF FULLERENE C60, A NEW FAMILY OF MEDICINAL NANOPARTICLES TO MEET THE FOLLOWING EXPECTATIONS: • Tissue-selective targeted delivery of 25Mg2+ paramagnetics to the porphyrin-signaling cell compartments in myocardium and, to a lesser degree, lymphocytes • The 25Mg2+-related magnetic isotope effect to promote a local and fast, jump-up increase of ATP production, even in the tissue oxygen deplete of any sort • Smart nanoparticles behavior while in Mt-membrane, i.e. a gradual 25Mg2+ release that occurs exclusively in response to the tissue hypoxia-caused metabolic acidosis • Low toxic, safe, efficient and completely eliminable (C60- clearing / porphyrin metabolizing) agents, all suitable for either short or long term administration schemes