SMARTDRUGENTITIES (239603)

  https://cordis.europa.eu/project/id/239603

  FP7 (2007-2013)

  Sophisticated Well-Targeted Therapeutic Entities based on Biologically Compatible Ti(IV) Active Cores and Building Blocks

  ERC Starting Grant - Materials and Synthesis (ERC-SG-PE5)

  gene therapy  ·  nanotechnology  ·  catalysis  ·  geometry

  2009-10-01 Start Date (YY-MM-DD)

  2014-09-30 End Date (YY-MM-DD)

  € 1,400,000 Total Cost

  Description

I propose to develop sophisticated anti-tumor agents targeted particularly to the location of activity. My team has recently introduced a new family of Ti(IV) complexes that demonstrates higher activity than known compounds with substantially higher stability and defined hydrolytic behavior, properties that were found to be essential. I propose to study various derivatives and identify the parameters affecting activity, including steric and electronic effects, enantiomeric purity, ligand lability etc., and elucidation various mechanistic aspects of reactivity. More importantly, I propose to construct pH-sensitive transport units that will allow protection of the sensitive active species throughout their delivery and release only near the target location based on the variable pH conditions of different human tissues. In particular, unique spherical molecules held together by metal-ligand interactions will be prepared. The building blocks will consist of the planar ligands of C3-axis bound to three biocompatible Ti(IV) ions each with defined angles and geometry. The resulting spherical compounds will be utilized to encapsulate the active complexes and release them upon hydrolysis at the desired pH based on the pH-dependent hydrolysis pattern already established for related compounds. Preliminary calculations have confirmed the possibility of forming these compounds, which are particularly matching in their expected size to encapsulate our complexes. Larger spheres will also be prepared as cavities for larger molecules, which may be linked together for the delivery of multiple drugs. These compounds may find applications in various areas where a protected environment or delivery of sensitive compounds is required, such as in gene therapy, nano-technology, and catalysis.

  Complicit Organisations

1 Israeli organisation participates in SMARTDRUGENTITIES.