Self-assembled peptide nanofibers demonstrate tunable CD38 avidity

CD38 is overexpressed in multiple myeloma (MM) cells and consequently an important clinical target for therapeutic antibodies. However, the utility of CD38-binding antibodies for imaging has been limited by unfavorable pharmacokinetics. Peptides offer a promising alternative due to their favorable biodistribution and modular design. In this study, we modified two phage-display-identified high specificity CD38-binding oligopeptide radiotracers by adding a lipid tail to facilitate self-assembly into nanofibers. The length of the lipid tail determines epitope packing, nanofiber morphology and, subsequently, binding to CD38. The self-assembly process additionally enables encapsulation of small-molecule therapeutics, which paves the way for future theranostic development. The resulting structures demonstrate excellent stability in serum and radiolabeling efficiency. Preliminary animal studies have shown no adverse effects at anticipated imaging dosages.