Materials-Based Strategies for Controlling the Route of Cell- and Tissue-Level Drug Delivery

A major challenge facing drug delivery is efficient targeting of bioactive cargo to specific cells or tissues. Delivery of macromolecular cargo (e.g., nucleic acids, proteins) to cells for example, is hindered by the inability of these therapeutics to escape endosomes following cell internalization, ultimately leading to cargo degradation. Additionally, directing cargo to the correct tissues (e.g., a tumor or infection site) is necessary for maximum drug efficacy and to minimize side effects. Thus, developing new clinically-relevant treatments requires drug delivery systems that address both cellular- and tissue-level barriers. This poster will describe several biomaterial-based strategies we are developing to overcome these challenges, emphasizing materials design and characterization. One strategy seeks to bypass endocytosis to achieve efficient cellular delivery of large, membrane-impermeable macromolecular cargo (e.g., DNA or RNA oligonucleotides) using cell-penetrating gold nanoparticle carriers that display amphiphilic mixed ligand shells composed of 11-mercapto-1-undecanesulphonate (MUS) and 1-octanethiol (OT). On a tissue-delivery level, in vivo strategies for increasing the localization and persistence of nucleic acids and small molecule vaccine components in secondary lymph organs – the key site of immune response generation – will be described. Polymeric particles displaying amphiphilic lipids as stabilizers at the polymer/aqueous interface allow controlled release of these vaccine components, and the ability to tune materials properties (e.g., size, aggregation control, biodistribution/kinetics) plays a critical role in vaccine effectiveness during in vivo studies with the polymeric vaccine particles.