3. MELITTIN’S ANTI ARTHIRITIC EFFECT ON SYNOVIAL CELLS Blocks expression of inflammatory genes = COX-2 inhibitor drugs used to treat RA. Inhibs the critical DNA binding activity of NF-kB(Nuclear Factor kappa B).
4. HARMFUL EFFECTS OF MELITTIN Fatal if enters the bloodstream Lyses the RBCs Cause allergic reactions which can act as a skin,eye or respiratory irritant.
5. ABSTRACT OF THE PAPERPAPER:"Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth,"RESEARCHER: SamuelWickline, M.D., principal investigator of the Siteman Center of Cancer Nanotechnology Excellence, and his Colleagues
9. Biological properties of cancer cells Acquisition of self-sufficiency in growth signals Loss of sensitivity to anti-growth signals Loss of capacity for apoptosis Loss of capacity for senescence, leading to limitless replicative potential (immortality)
10. Acquisition of sustained angiogenesis, allowing the tumor to grow beyond the limitations of passive nutrient diffusion. Acquisition of ability to invade neighbouringtissues, the defining property of invasive carcinoma. Acquisition of ability to build metastases at distant sites, the classical property of malignant tumors (carcinomas or others).
14. LYTIC ACTIVITY OF MELITTIN Hydrophobic inner surface of a melittin helix may integrate into the a polar region of a bilayer with the helix axis Hydrophilic surface is exposed to the aqueous phase. Partitions into the cell membranes as a monomer oligomerizationinto toroidal or barrel stave structures
15. Partitions into the cell membranes as a monomer oligomerization into toroidal or barrel stave structures
16. NANOPARITCLES Synthetic delivery vehicle to deliver melittin intravenously Stable towards the lytic action of Melittin Deposit their cargo of melittin, which rapidly merges with the target cells.
25. STEP 1 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
26. Delivery of melittin from integrin αvβ3–targeted nanoparticles to endothelial cells and cancer cells Selected higher magnification platinum replica images of nanoparticles on the plasma membrane and microvilliof C32 melanoma cells
27. STEP 2 Melittin that are inserted in the nanoparticle monolayer then diffuse along the continuous hemi fusion pore
28. STEP 3 Cytochrome c release from the mitochondria of tumor cells and apoptosis
29. WHAT IS DIFFERENT ABOUT THIS THERAPY? The mechanism by which it kills cells does not trigger the drug resistance that often develops with conventional anticancer therapies. Cancer cells can adapt and develop resistance to many anticancer agents that alter gene function or target a cell's DNA. But it's hard for cells to find a way around the mechanism that melittin uses to kill