Events at the nanoscale are governed by distinct cellular, biochemical and biophysical processes that are not experienced by small molecule drugs. For example, nanoscale objects adsorb dynamic layers of proteins on their surfaces known as the “protein corona”; are large enough for their surface ligand valency to influence cell receptor interactions; and are primarily cleared from circulation by innate immune cells that have evolved to interact with and collect nanoscale particulates like viruses, apoptotic bodies and extracellular vesicles. Understanding how phenomena at the bio/nano interface of nanocarriers, biological fluids and innate immune cells influence the stability, assembly and therapeutic targeting of soft nanobiomaterials is thus critical for their applications in drug delivery.

Here, we will discuss synthetic platforms that we have developed for enhanced targeting of immune cell subsets, sustained delivery of drug loaded nanobiomaterials, and highly efficient multi-drug encapsulation of water-soluble payloads such as proteins, peptides and nucleic acids. In addition to achieving controlled targeting and modulation of the immune cells, our focus on the bio/nano interface during the rational design and engineering of nanobiomaterials has led to therapeutic applications in a variety of other areas, including vaccination against infectious disease, glaucoma, cancer immunotherapy, and diabetes.

<b>Figure <i>1</i>. Nanobiomaterial surface chemistry modulates the conformation of adsorbed albumin and alters nanocarrier clearance by macrophage class A1 scavenger receptors. </b>(<b>A<i>, B</i></b>) <i>Poly(ethylene glycol)-</i>b<i>-poly(propylene sulfide) </i>polymersomes (PS) of different surface chemistries<i> adsorb distinct protein corona. </i> (<b>C<i>-E</i></b>) Overview of <i>nanobiomaterial</i> biodistribution study in C57BL/6J mice (n = 5<i>).</i> (<b>F</b>) The percentage a-helicity of albumin following adsorption to different nanocarrier surfaces. (<b>G, <i>H</i></b>) Only <i>m</i>acrophages with fucoidan (SR-A1 competitor) decrease uptake of PS for albumin-denaturing surfaces<i>. </i>

Figure 1. Nanobiomaterial surface chemistry modulates the conformation of adsorbed albumin and alters nanocarrier clearance by macrophage class A1 scavenger receptors. (A, B) Poly(ethylene glycol)-b-poly(propylene sulfide) polymersomes (PS) of different surface chemistries adsorb distinct protein corona. (C-E) Overview of nanobiomaterial biodistribution study in C57BL/6J mice (n = 5). (F) The percentage a-helicity of albumin following adsorption to different nanocarrier surfaces. (G, H) Only macrophages with fucoidan (SR-A1 competitor) decrease uptake of PS for albumin-denaturing surfaces.

Monica Olvera de la Cruz

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