Lipidated poly(amino acid) nanostructures as versatile therapeutic delivery vehicles

Abstract

Poly(amino acid)s are a diverse and capable class of polymers with significant potential for utilization in a wide variety of drug delivery applications. A sub-class of these biomaterials known as lipidated poly(amino acid)s (LPAAs) are amphiphiles composed of both hydrophobic and hydrophilic domains yielding interesting physical properties. In this article, we describe our efforts in developing a novel class of lysine and valine containing LPAAs synthesized via hexadecylamine initiated N-carboxyanhydride ring-opening polymerization (NCA-ROP). These highly hydrophobic LPAAs were found capable of undergoing hydrophobically-driven self-assembly into small nanostructures as well as being forced into larger nanostructures using a novel dump-and-stir nanoprecipitation process. This process yielded fine control over resulting nanoparticle size and cargo entrapment. Furthermore, cell-targeting DNA aptamer modification of doxorubicin-loaded LPAA nanoparticles induced significant death of co-incubated Non-Hodgkin Lymphoma cells providing exciting evidence of the therapeutic potential of this novel biomaterials-based delivery device.