Yu Tian1,James LaBelle1,Matthew Tirrell1
University of Chicago1
Yu Tian1,James LaBelle1,Matthew Tirrell1
University of Chicago1
In cancer treatment, drugs can be categorized into two types, small molecules and biologicals. Therefore, it leaves a gap in the size of the druggable therapeutic targets. While next-genetration peptides fall in this size range can potentially be developed into new class of drugs. However, preclinical peptide therapeutics generally have low in vivo efficacy due to poor cell permeability and high proteolysis sensitivity. By attaching hydrophobic moieties to therapeutic peptides, the conjugated peptidic amphiphilic compounds can self-assemble into micelles with some physicochemical properties analogous to proteins. Because of the high chemical versatility of peptides, such a design of protein analogous micelle system can be highly modular to achieve the cell permeability, targeting capability, and combined delivery of multiple therapeutics at the same time. In this work, therapeutic peptides targeting intracellular p53 pathway and BCL-2 family proteins are chemically modified as peptide amphiphiles to formulate into protein analogous micelles. <i>In vitro</i> mechanism of action and cellular trafficking processes were investigated in wild type p53 DLBCL cell lines, providing guidelines for next generation micelle design.