For the past two decades, block copolymers have proven to be excellent candidates for providing well-define self-assembled nanostructures. However, they possess nearly no biological function as compared with natural biomacromolecules such as proteins that offer enormous diversities in terms of activity and conformation. By combining the self-assembling propensities of block copolymers together with the richness of function-bearing peptides or protein domains, we aim at creating functional hybrid nanoscale machines integrating the advantages of both materials. The Tat47-57 sequence (YGRKKRRQRRR) from the HIV-1 TAT protein is a hydrophilic peptide presenting tremendous cell penetrating ability as well as blood-brain barrier crossing capabilities.[1] Poly(trimethylene carbonate) (PTMC) is a biocompatible hydrophobic polymer segment with compelling self-assembly properties.[2] Amphiphilic Tat-b-PTMC molecular chimeras with tunable hydrophilic fractions were synthesized with high molecular precision and thoroughly characterized (DOSY NMR, MALDI-MS). By direct dissolution in aqueous buffer, Tat-b-PTMC self-assembled into size-tunable, highly monodisperse core-shell nanometer-sized particles, presenting a fully-coated Tat corona.[3] Their physico-chemical profiles were assessed by complementary imaging (AFM, TEM) and scattering techniques (multiangle DLS, SANS) and correlated with their molecular architectures as well as their biological features (transduction efficiency and toxicity on HeLa cells).[1] Viv�s, 1997, Journal of Biological Chemistry, 272, 16010-16017.[2] Sanson, 2011, ACS Nano, 5, 1122-1140.[3] Drappier, 2013, Polymer Chemistry, 4, 2011-2018

Cell-penetrating micelles from amphiphilic peptide-<i>b</i>-polymer chimeras: From molecular structure to biological features

246th National Meeting (2013)

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Cell-penetrating micelles from amphiphilic peptide-b-polymer chimeras: From molecular structure to biological features