This thesis work deals with preparation and study of cell-penetrating self-assemblies from amphiphilicpolymer-b-peptide Tat-b-poly(trimethylene carbonate) conjugates. Tat-b-PTMC chimeras withtunable hydrophilic fractions were synthesized, thoroughly characterized and self-assembled inaqueous buffer into size-tunable, highly monodisperse core-shell nanoparticles, presenting a full Tatcorona. Their physico-chemical profiles were assessed by complementary imaging (AFM, TEM) andscattering techniques (multiangle DLS, SANS) and correlated with their molecular architectures.Their transduction ability in vitro on HeLa cells and interaction mode with phospholipid membraneswere studied with a view to correlate their physico-chemical profiles with their biological properties.This interdisciplinary approach partially shed light on the interactions at play in the cellular uptakeprocess. With the ultimate goal of improving pharmacological characteristics, we finally endeavoredto develop an ON/OFF PEGylation strategy to harness the cell penetrating power of thosebiomacromolecular self-assembled systems.
