[Todos] Seminario DQIAQF_INQUIMAE_Martes_18_08

[Mireille Perec]

SEMINARIO DQIAFQ-INQUIMAE

 

 

Martes 18 de Agosto 13 hs

Aula Seminarios INQUIMAE

Ciudad Universitaria Pab. II  Piso 3°

 

 

Professor Igal Szleifer

Department of Biomedical Engineering, Department of Chemistry,  Department of Biological and Chemical Engineering
Northwestern University





Targeted delivery of lipid agents and nanoparticles to cancer cells: 
How to combine chemical reaction equilibrium and physical interactions for biological activity




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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