Smart Nano-objects for Alteration of Lipid bilayers (SNAL) Initial Training Network is a multidisciplinary EU-funded 7th Framework Programme specially designed to provide scientific and transferable skill training and career development for early stage researchers and experienced researchers in the field of lipid research.

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ESR5-L: Synthesis and characterization of functional biomimetic polymers for intracellular delivery

Chemical synthesis, characterisation of polymers and nano-objects

Objectives

This project is focused on development of functional biomimetic polymers which can traverse across cellular membranes to deliver payloads into the cell interior.

  • Synthesis and characterization of pH-responsive, membrane-active polymers.
  • Preparation of therapeutic nanoparticles incorporating chemotherapeutic agents or biological molecules.
  • Understanding and controlling of the trafficking of polymers into a model cellular system.
  • Demonstration and optimization of delivery of payload into the cell interior.

Tasks and methodology

  • Characterization of polymer structure and composition by FTIR and NMR; measurement of polymer molecular weight and polydispersity by GPC.
  • Appropriate method (e.g. cleavable conjugation, physical complexation or encapsulation) for payload incorporation.
  • Appropriate analytical techniques (such as UV-visible spectroscopy, fluorescence spectroscopy, DLS, zeta potential analyzer) for investigation into conformational characteristics, size and charge.
  • Evaluation of membrane activity using a haemolysis model and/or LDH assay.
  • Investigation into intracellular trafficking and delivery efficiency by confocal microscopy and flow cytometry and measurement of cytotoxicity by MTT or Alamar Blue assay.

Details

Specifically, I would like to synthesize hyper-branched pH-responsive poly(L-lysine isophthalamide) and its derivatives (See Scheme below).  I believe that the combination of hyper-branched topological structure and pH-responsive metabolite-derived polyamide could generate stimulating materials as a novel drug delivery system. Since hyper-branched poly(L-lysine isophthalamide) (HPLP) and its derivatives have similar architecture as globular protein, they might have excellent biocompatibility and low toxicity. What’s more, HPLP have a great number of amine end groups, which could be easily modified with functional molecules to achieve better solubility as well as targeting effects. With these amine end groups and carboxyl side groups, the pH-responsiveness might be highly adjustable. Furthermore, it’s quite easy to prepare such polymers by one-pot condensation procedure and to purify by simple precipitation. All these advantages make it an ideal drug carrier for biological systems.

SCHEME_Shiqi

Starting date

September 2014

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    Shiqi Wang

    MSCA Early Stage Researcher at Imperial College London, UK Synthesis of polymers and nanoparticles for translocation through lipid bilayers, more...
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