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align=center><B><SPAN lang=PT-BR
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial; mso-ansi-language: PT-BR">SEMINARIO
DQIAFQ-INQUIMAE</SPAN></B><SPAN lang=PT-BR
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align=center><B><U><SPAN lang=PT-BR
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial; mso-ansi-language: PT-BR">Martes 18
de Agosto 13 hs<o:p></o:p></SPAN></U></B></P>
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align=center><B><SPAN
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial; mso-ansi-language: ES">Aula
Seminarios INQUIMAE</SPAN></B><SPAN lang=ES-TRAD
style="FONT-SIZE: 16pt; FONT-FAMILY: Arial; mso-ansi-language: ES-TRAD"><o:p></o:p></SPAN></P>
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align=center><B><SPAN lang=EN-US
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial">Ciudad Universitaria Pab. II<SPAN
style="mso-spacerun: yes"> </SPAN>Piso 3</SPAN></B><B><SPAN
style="FONT-SIZE: 12pt; FONT-FAMILY: Symbol; mso-ansi-language: ES; mso-bidi-font-family: Arial; mso-ascii-font-family: Arial; mso-hansi-font-family: Arial; mso-char-type: symbol; mso-symbol-font-family: Symbol"><SPAN
style="mso-char-type: symbol; mso-symbol-font-family: Symbol">°</SPAN></SPAN></B><B><SPAN
lang=EN-US
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial"><o:p></o:p></SPAN></B></P>
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align=center><B><SPAN lang=EN-US
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial"><o:p> </o:p></SPAN></B></P>
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align=center><B><SPAN lang=EN-US
style="FONT-SIZE: 14pt; FONT-FAMILY: Arial">Professor Igal
Szleifer</SPAN></B><SPAN lang=EN-US
style="FONT-SIZE: 14pt; FONT-FAMILY: 'Courier New'"><o:p></o:p></SPAN></P>
<P class=MsoNormal
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align=center><SPAN lang=EN-GB
style="FONT-SIZE: 10pt; FONT-FAMILY: Arial; mso-ansi-language: EN-GB">Department
of Biomedical Engineering, Department of Chemistry,<SPAN
style="mso-spacerun: yes"> </SPAN>Department of Biological and Chemical
Engineering<BR>Northwestern University</SPAN><SPAN lang=EN-US
style="FONT-SIZE: 8pt; FONT-FAMILY: 'Courier New'"><BR><BR></SPAN><SPAN
lang=EN-US style="FONT-SIZE: 12pt; FONT-FAMILY: 'Courier New'"><BR
style="mso-special-character: line-break"><BR
style="mso-special-character: line-break"></SPAN><SPAN lang=EN-US
style="FONT-SIZE: 10pt; FONT-FAMILY: 'Courier New'"><o:p></o:p></SPAN></P>
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align=center><B><I><SPAN lang=EN-US
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial">Targeted delivery of lipid agents
and nanoparticles to cancer cells: <BR>How to combine chemical reaction
equilibrium and physical interactions for biological
activity</SPAN></I></B><SPAN lang=EN-US
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial"><BR><BR
style="mso-special-character: line-break"><BR
style="mso-special-character: line-break"></SPAN><SPAN lang=EN-US
style="FONT-SIZE: 12pt; FONT-FAMILY: 'Courier New'"><o:p></o:p></SPAN></P>
<P class=MsoNormal
style="MARGIN: 0cm 0cm 0pt 35.4pt; tab-stops: 45.8pt 91.6pt 137.4pt 183.2pt 229.0pt 274.8pt 320.6pt 366.4pt 412.2pt 458.0pt 503.8pt 549.6pt 595.4pt 641.2pt 687.0pt 732.8pt"><SPAN
lang=EN-US
style="FONT-SIZE: 10pt; FONT-FAMILY: Arial; mso-bidi-font-weight: bold">One of
the major challenges in drug delivery is the ability to target exclusively sick
cells without<SPAN style="mso-spacerun: yes"> </SPAN>interacting<SPAN
style="mso-spacerun: yes"> </SPAN>with<SPAN
style="mso-spacerun: yes"> </SPAN>healthy<SPAN
style="mso-spacerun: yes"> </SPAN>cells.<SPAN
style="mso-spacerun: yes"> </SPAN>This<SPAN
style="mso-spacerun: yes"> </SPAN>is<SPAN style="mso-spacerun: yes">
</SPAN>particularly<SPAN style="mso-spacerun: yes"> </SPAN>important<SPAN
style="mso-spacerun: yes"> </SPAN>for<SPAN
style="mso-spacerun: yes"> </SPAN>cancer<SPAN
style="mso-spacerun: yes"> </SPAN>drug delivery.<SPAN
style="mso-spacerun: yes"> </SPAN>In this presentation we<SPAN
style="mso-spacerun: yes"> </SPAN>show<SPAN
style="mso-spacerun: yes"> </SPAN>how <SPAN
style="mso-spacerun: yes"> </SPAN>we can take<SPAN
style="mso-spacerun: yes"> </SPAN>advantage<SPAN
style="mso-spacerun: yes"> </SPAN>of the modification that<SPAN
style="mso-spacerun: yes"> </SPAN>occur<SPAN
style="mso-spacerun: yes"> </SPAN>on<SPAN style="mso-spacerun: yes">
</SPAN>the<SPAN style="mso-spacerun: yes"> </SPAN>plasma<SPAN
style="mso-spacerun: yes"> </SPAN>membrane<SPAN
style="mso-spacerun: yes"> </SPAN>of<SPAN style="mso-spacerun: yes">
</SPAN>cancer<SPAN style="mso-spacerun: yes"> </SPAN>cells<SPAN
style="mso-spacerun: yes"> </SPAN>to<SPAN style="mso-spacerun: yes">
</SPAN>target<SPAN style="mso-spacerun: yes"> </SPAN>surface<SPAN
style="mso-spacerun: yes"> </SPAN>modified nanoparticles. The basic idea
is to take advantage of the over-expressed receptors and the different lipid
composition of the plasma membrane<SPAN style="mso-spacerun: yes">
</SPAN>in (some) cancer cells. To this end we<SPAN
style="mso-spacerun: yes"> </SPAN>show,<SPAN
style="mso-spacerun: yes"> </SPAN>as<SPAN style="mso-spacerun: yes">
</SPAN>a<SPAN style="mso-spacerun: yes"> </SPAN>proof<SPAN
style="mso-spacerun: yes"> </SPAN>of<SPAN style="mso-spacerun: yes">
</SPAN>concept,<SPAN style="mso-spacerun: yes"> </SPAN>how<SPAN
style="mso-spacerun: yes"> </SPAN>modifying the<SPAN
style="mso-spacerun: yes"> </SPAN>surface of<SPAN
style="mso-spacerun: yes"> </SPAN>the<SPAN
style="mso-spacerun: yes"> </SPAN>nanoparticles<SPAN
style="mso-spacerun: yes"> </SPAN>with binary<SPAN
style="mso-spacerun: yes"> </SPAN>mixtures<SPAN
style="mso-spacerun: yes"> </SPAN>of<SPAN style="mso-spacerun: yes">
</SPAN>short<SPAN style="mso-spacerun: yes"> </SPAN>polymers<SPAN
style="mso-spacerun: yes"> </SPAN>can<SPAN
style="mso-spacerun: yes"> </SPAN>increase<SPAN
style="mso-spacerun: yes"> </SPAN>the<SPAN
style="mso-spacerun: yes"> </SPAN>binding<SPAN
style="mso-spacerun: yes"> </SPAN>to<SPAN style="mso-spacerun: yes">
</SPAN>the<SPAN style="mso-spacerun: yes"> </SPAN>cells<SPAN
style="mso-spacerun: yes"> </SPAN>by<SPAN style="mso-spacerun: yes">
</SPAN>orders<SPAN style="mso-spacerun: yes"> </SPAN>of magnitude.
One<SPAN style="mso-spacerun: yes"> </SPAN>of the polymers<SPAN
style="mso-spacerun: yes"> </SPAN>in<SPAN style="mso-spacerun: yes">
</SPAN>the<SPAN style="mso-spacerun: yes"> </SPAN>mixture<SPAN
style="mso-spacerun: yes"> </SPAN>is aimed<SPAN
style="mso-spacerun: yes"> </SPAN>at protecting the<SPAN
style="mso-spacerun: yes"> </SPAN>nanoparticle and the other is a polybase
with a functional ligand as its end-group that specific targets the<SPAN
style="mso-spacerun: yes"> </SPAN>overexpressed<SPAN
style="mso-spacerun: yes"> </SPAN>receptors<SPAN
style="mso-spacerun: yes"> </SPAN>in<SPAN style="mso-spacerun: yes">
</SPAN>the<SPAN style="mso-spacerun: yes"> </SPAN>cancer<SPAN
style="mso-spacerun: yes"> </SPAN>cell.<SPAN
style="mso-spacerun: yes"> </SPAN>We<SPAN style="mso-spacerun: yes">
</SPAN>show<SPAN style="mso-spacerun: yes"> </SPAN>how<SPAN
style="mso-spacerun: yes"> </SPAN>the<SPAN
style="mso-spacerun: yes"> </SPAN>combination<SPAN
style="mso-spacerun: yes"> </SPAN>of electrostatic<SPAN
style="mso-spacerun: yes"> </SPAN>interactions,<SPAN
style="mso-spacerun: yes"> </SPAN>specific<SPAN
style="mso-spacerun: yes"> </SPAN>binding,<SPAN
style="mso-spacerun: yes"> </SPAN>acid-base<SPAN
style="mso-spacerun: yes"> </SPAN>equilibrium<SPAN
style="mso-spacerun: yes"> </SPAN>and<SPAN
style="mso-spacerun: yes"> </SPAN>molecular organization<SPAN
style="mso-spacerun: yes"> </SPAN>in<SPAN style="mso-spacerun: yes">
</SPAN>the<SPAN style="mso-spacerun: yes"> </SPAN>nanoparticle<SPAN
style="mso-spacerun: yes"> </SPAN>and<SPAN
style="mso-spacerun: yes"> </SPAN>on<SPAN style="mso-spacerun: yes">
</SPAN>the<SPAN style="mso-spacerun: yes"> </SPAN>lipid<SPAN
style="mso-spacerun: yes"> </SPAN>layer<SPAN
style="mso-spacerun: yes"> </SPAN>provides<SPAN
style="mso-spacerun: yes"> </SPAN>for<SPAN
style="mso-spacerun: yes"> </SPAN>a<SPAN style="mso-spacerun: yes">
</SPAN>non-trivial synergetic<SPAN style="mso-spacerun: yes">
</SPAN>effect<SPAN style="mso-spacerun: yes"> </SPAN>with<SPAN
style="mso-spacerun: yes"> </SPAN>highly<SPAN
style="mso-spacerun: yes"> </SPAN>improved<SPAN
style="mso-spacerun: yes"> </SPAN>binding<SPAN
style="mso-spacerun: yes"> </SPAN>capabilities.<SPAN
style="mso-spacerun: yes"> </SPAN>We<SPAN style="mso-spacerun: yes">
</SPAN>will<SPAN style="mso-spacerun: yes"> </SPAN>show<SPAN
style="mso-spacerun: yes"> </SPAN>how<SPAN
style="mso-spacerun: yes"> </SPAN>the approach<SPAN
style="mso-spacerun: yes"> </SPAN>of<SPAN style="mso-spacerun: yes">
</SPAN>the<SPAN style="mso-spacerun: yes"> </SPAN>nanoparticle<SPAN
style="mso-spacerun: yes"> </SPAN>to<SPAN style="mso-spacerun: yes">
</SPAN>the<SPAN style="mso-spacerun: yes"> </SPAN>lipid<SPAN
style="mso-spacerun: yes"> </SPAN>layer<SPAN
style="mso-spacerun: yes"> </SPAN>results<SPAN
style="mso-spacerun: yes"> </SPAN>in<SPAN style="mso-spacerun: yes">
</SPAN>a<SPAN style="mso-spacerun: yes"> </SPAN>highly<SPAN
style="mso-spacerun: yes"> </SPAN>inhomogeneous segregation<SPAN
style="mso-spacerun: yes"> </SPAN>of<SPAN style="mso-spacerun: yes">
</SPAN>lipids<SPAN style="mso-spacerun: yes"> </SPAN>in<SPAN
style="mso-spacerun: yes"> </SPAN>the<SPAN
style="mso-spacerun: yes"> </SPAN>cell<SPAN
style="mso-spacerun: yes"> </SPAN>membrane<SPAN
style="mso-spacerun: yes"> </SPAN>and<SPAN
style="mso-spacerun: yes"> </SPAN>of<SPAN style="mso-spacerun: yes">
</SPAN>polymers<SPAN style="mso-spacerun: yes"> </SPAN>in<SPAN
style="mso-spacerun: yes"> </SPAN>the<SPAN
style="mso-spacerun: yes"> </SPAN>nanoparticle.<SPAN
style="mso-spacerun: yes"> </SPAN>The molecular<SPAN
style="mso-spacerun: yes"> </SPAN>segregation<SPAN
style="mso-spacerun: yes"> </SPAN>can<SPAN
style="mso-spacerun: yes"> </SPAN>be<SPAN style="mso-spacerun: yes">
</SPAN>used<SPAN style="mso-spacerun: yes"> </SPAN>as<SPAN
style="mso-spacerun: yes"> </SPAN>a<SPAN style="mso-spacerun: yes">
</SPAN>tool<SPAN style="mso-spacerun: yes"> </SPAN>not<SPAN
style="mso-spacerun: yes"> </SPAN>only<SPAN
style="mso-spacerun: yes"> </SPAN>for<SPAN
style="mso-spacerun: yes"> </SPAN>drug<SPAN
style="mso-spacerun: yes"> </SPAN>delivery<SPAN
style="mso-spacerun: yes"> </SPAN>but<SPAN
style="mso-spacerun: yes"> </SPAN>also<SPAN
style="mso-spacerun: yes"> </SPAN>for molecular recognition of surface
domains. The implication of our findings in terms of the complex<SPAN
style="mso-spacerun: yes"> </SPAN>non-additive interplay between<SPAN
style="mso-spacerun: yes"> </SPAN>chemical reactions<SPAN
style="mso-spacerun: yes"> </SPAN>and physical interactions<SPAN
style="mso-spacerun: yes"> </SPAN>in highly inhomogeneous
environments<SPAN style="mso-spacerun: yes"> </SPAN>to the design of
responsive systems as well as the fundamental understanding of molecular cell
biology will be discussed.<BR></SPAN><SPAN lang=EN-US
style="FONT-SIZE: 12pt; FONT-FAMILY: Arial; mso-bidi-font-weight: bold"><SPAN
style="mso-spacerun: yes"> </SPAN></SPAN><SPAN lang=EN-US
style="FONT-SIZE: 10pt; FONT-FAMILY: Arial; mso-bidi-font-weight: bold"><o:p></o:p></SPAN></P>
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