(36h) Albumin Nanovectors with Tunable Size and Hydrophilicity As a Precursor to Bifunctional Colloids

The success of albumin-bound chemotherapeutics has demonstrated the protein's value as a nonimmunogenic drug platform, significantly boosting residence time compared to naked drugs. One emerging area of research is in bispecific recognition, wherein a single drug particle can bind cancer cells to immune cells and trigger the beginning of an acquired immune response. However, many of these novel treatments suffer from poor bioavailability and low stability, and the necessity of a nanocarrier that maintains the bifunctional morphology is clear. To achieve directionally constrained bifunctional behavior, this research seeks to synthesize "bilobal" particles where a lipophilic sphere is self-assembled onto a previously synthesized hydrophilic sphere. While synthetic bilobal colloids are well known, there are no known examples of biocompatible bilobal colloid-based proteins such as albumin suitable for in-vivo application. We are synthesizing albumin particles with anisotropy in both shape and surface chemistry allowing for multidentate functionalization of “lobes” independently of one another. Progress to date has optimized synthesis of hydrophilic albumin nanospheres using green chemistry and multiple crosslinkers under ambient conditions, as well as ligand functionalization that alters the hydrophilicity of albumin and provides different binding sites for later conjugations. The aging studies conducted on the synthesized particles illustrated that they are colloidally stable even in biologically isotonic electrolytic conditions for over six months. Manipulation of electrolyte concentrations and ligand concentrations allow for independent control of size, polydispersity, and zeta potential.