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Seminar On Melittin


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Seminar On Melittin

  2. 2. BEE VENOM<br />Apismeliffera<br />Human Hands<br />Melittin-Toxin in the bee venom<br />
  3. 3. MELITTIN’S ANTI ARTHIRITIC EFFECT ON SYNOVIAL CELLS<br />Blocks expression of inflammatory genes = COX-2 inhibitor drugs used to treat RA. <br />Inhibs the critical DNA binding activity of NF-kB(Nuclear Factor kappa B). <br />
  4. 4. HARMFUL EFFECTS OF MELITTIN<br />Fatal if enters the bloodstream<br />Lyses the RBCs<br />Cause allergic reactions which can act as a skin,eye or respiratory irritant.<br />
  5. 5. ABSTRACT OF THE PAPERPAPER:&quot;Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth,&quot;RESEARCHER: SamuelWickline, M.D., principal investigator of the Siteman Center of Cancer Nanotechnology Excellence, and his Colleagues<br />
  6. 6. WHAT IS CANCER?<br />Medical term: malignantneoplasm<br />A group of cellsdisplay<br /><ul><li>uncontrolled growth
  7. 7. invasion (intrusion on and destruction of adjacent tissues)
  8. 8. metastasis (spread to other locations in the body via lymph or blood). </li></li></ul><li>Cancer Tumors<br />Formation Of Cancer Cells<br />
  9. 9. Biological properties of cancer cells<br />Acquisition of self-sufficiency in growth signals<br />Loss of sensitivity to anti-growth signals<br />Loss of capacity for apoptosis<br />Loss of capacity for senescence, leading to limitless replicative potential (immortality) <br />
  10. 10. Acquisition of sustained angiogenesis, allowing the tumor to grow beyond the limitations of passive nutrient diffusion. <br />Acquisition of ability to invade neighbouringtissues, the defining property of invasive carcinoma. <br />Acquisition of ability to build metastases at distant sites, the classical property of malignant tumors (carcinomas or others). <br />
  11. 11. WHAT ISMELITTIN?<br />water-soluble cationic amphipathic 26-aa α-helical peptide with the sequence GIGAVLKVLTTGLPALISWIKRKRQQ<br /><ul><li>nonspecific cytolytic peptide that attacks all lipid membranes
  12. 12. Powerful stimualator of phospholipase A2 </li></li></ul><li>STRUCTURE OF MELITTIN<br />in aqueous salt solutions it exists as a tetramer. <br />Bent alpha-helical rod<br />Inner surface consists of hydrophobic sidechains<br />Outer surface consistof hydrophilic side chains.<br /> helix is strongly amphiphilic<br />
  13. 13. Melittin tetramer–monomer (×4) transition<br />©2009 by National Academy of Sciences<br />
  14. 14. LYTIC ACTIVITY OF MELITTIN<br />Hydrophobic inner surface of a melittin helix may integrate into the a polar region of a bilayer with the helix axis <br />Hydrophilic surface is exposed to the aqueous phase.<br />Partitions into the cell membranes as a monomer <br />oligomerizationinto toroidal or barrel stave structures<br />
  15. 15. Partitions into the cell membranes as a monomer<br />oligomerization into toroidal or barrel stave structures <br />
  16. 16. NANOPARITCLES<br />Synthetic delivery vehicle to deliver melittin intravenously<br />Stable towards the lytic action of Melittin<br />Deposit their cargo of melittin, which rapidly merges with the target cells.<br />
  17. 17. SYNTHESIS OF NANOPARTICLES<br />Nanovehicle carriers were synthesized as an oil-in-water emulsion by microfuidization<br />Incorporated 0.1 mole% peptidomimeticvitronectin antagonist conjugated to polyethylene glycol 2000–phosphatidylethanolamine<br />COMPOSITION<br /><ul><li>Perfluorocarbon core
  18. 18. Monolayer of phospholipid</li></li></ul><li>ADVANTAGES OF NANOPARTICLEENCAPSULATION<br /><ul><li>Created an antitumor drug with suitable safety and pharmacological properties.
  19. 19. Spared red blood cells and other tissues from any damage by the lytic activity of melttin.</li></li></ul><li>TYPES OF EXPREIMENTAL TUMORS<br />Syngeneic (B16F10 mouse melanoma),<br />Xenograft (MDA-MB-435 human breast cancer)<br />Precancerous lesions in K14-HPV16 mice with squamous dysplasia and carcinoma<br />
  21. 21.
  23. 23. RBCs
  25. 25. STEP 1<br />Specific targeting to cancer cells by the incorporation of mimetic targeting ligands that leads to the binding, close apposition, and hemifusion of the lipid monolayer with the targeted cell lipid membrane <br />
  26. 26. Delivery of melittin from integrin αvβ3–targeted nanoparticles to endothelial cells and cancer cells <br />Selected higher magnification platinum replica images of nanoparticles on the plasma membrane and microvilliof C32 melanoma cells <br />
  27. 27. STEP 2<br />Melittin that are inserted in the nanoparticle monolayer then diffuse along the continuous hemi fusion pore <br />
  28. 28. STEP 3<br />Cytochrome c release from the mitochondria of tumor cells and apoptosis <br />
  29. 29. WHAT IS DIFFERENT ABOUT THIS THERAPY?<br />The mechanism by which it kills cells does not trigger the drug resistance that often develops with conventional anticancer therapies. <br />Cancer cells can adapt and develop resistance to many anticancer agents that alter gene function or target a cell&apos;s DNA.<br />But it&apos;s hard for cells to find a way around the mechanism that melittin uses to kill <br />
  30. 30. THANK YOU<br />