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Design of Thermo-Responsive Self-Assembly of PEGylated Fatty Acids: Switching Reversibly from Tubes or Vesicles to Micelles at Physiological Temperature

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In drug delivery, it is of utmost importance to render the nanocarriers “stealth” in order to prevent protein adsorption from physiological fluids, otherwise a protein corona will grow rapidly around them and will drive their in vivo biological fate. To this goal, the most widespread strategy consists in decorating nanocarriers with a protective polymeric shell of poly(ethylene glycol) (PEG) chains.

We present here a simple and robust one-pot route to design thermo-responsive PEGylated self-assemblies of fatty acids into two morphology types at room temperature, multi-lamellar tubes or vesicles, which transit reversibly upon heating into small ellipsoidal micelles around physiological temperature, as demonstrated by Small Angle Neutron Scattering. It is based on the controlled insertion of various PEG chains end-capped by fatty acid moieties into self-assemblies of 12-hydroxy stearic acid, a bio-based green surfactant.

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