[Todos] Fw: [Todos QI] SEMINARIO 18_08_09 DQIAQF_INQUIMAE

[Mireille Perec]

Dr                                                       SEMINARIOS DQIAQF/ INQUIMAE 2009
                                                         

                                                        MARTES 18 de Agosto de 2009-13hs

                                     

                                                         Aula de Seminarios del INQUIMAE, Pab. II Piso 3



      Dr. Igal Szleifer
     

      Department of Biomedical Engineering
     

      Department of Chemistry
     

      Department of Biological and Chemical Engineering
     

      Northwestern University
     

      Evanston, IL 60208
     







      One of the major challenges in drug delivery is the ability to target exclusively sick cells
     

      without  interacting  with  healthy  cells.  This  is  particularly  important  for  cancer  drug
     

      delivery.  In this presentation we  show  how  we can take  advantage  of the  modification
     

      that  occur  on  the  plasma  membrane  of  cancer  cells  to  target  surface  modified
     

      nanoparticles. The basic idea is to take advantage of the over-expressed receptors and the
     

      different lipid composition of the plasma membrane  in (some) cancer cells. To this end
     

      we  show,  as  a  proof  of  concept,  how  modifying the  surface of  the  nanoparticles  with
     

      binary  mixtures  of  short  polymers  can  increase  the  binding  to  the  cells  by  orders  of
     

      magnitude. One  of the polymers  in  the  mixture  is aimed  at protecting the  nanoparticle
     

      and the other is a polybase with a functional ligand as its end-group that specific targets
     

      the  overexpressed  receptors  in  the  cancer  cell.  We  show  how  the  combination  of
     

      electrostatic  interactions,  specific  binding,  acid-base  equilibrium  and  molecular
     

      organization  in  the  nanoparticle  and  on  the  lipid  layer  provides  for  a  non-trivial
     

      synergetic  effect  with  highly  improved  binding  capabilities.  We  will  show  how  the
     

      approach  of  the  nanoparticle  to  the  lipid  layer  results  in  a  highly  inhomogeneous
     

      segregation  of  lipids  in  the  cell  membrane  and  of  polymers  in  the  nanoparticle.  The
     

      molecular  segregation  can  be  used  as  a  tool  not  only  for  drug  delivery  but  also  for
     

      molecular recognition of surface domains. The implication of our findings in terms of the
     

      complex  non-additive interplay between  chemical reactions  and physical interactions  in
     

      highly inhomogeneous environments  to the design of responsive systems as well as the
     

      fundamental understanding of molecular cell biology will be discussed.
     

 

 

                                                                           
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