Tumor-specific intracellular delivery: peptide-guided transport of a catalytic toxin.

ABSTRACT: There continues to be a need for cancer-specific ligands that can deliver a wide variety of therapeutic cargos. Ligands demonstrating both tumor-specificity and the ability to mediate efficient cellular uptake of a therapeutic are critical to expand targeted therapies. We previously reported the selection of a peptide from a peptide library using a non-small cell lung cancer (NSCLC) cell line as the target. Here we optimize our lead peptide by a series of chemical modifications including truncations, N-terminal capping, and changes in valency. The resultant 10 amino acid peptide has an affinity of <40 nM on four different NSCLC cell lines as a monomer and is stable in human serum for >48 h. The peptide rapidly internalizes upon cell binding and traffics to the lysosome. The peptide homes t

SUBMITTER: Allred CA 

PROVIDER: S-EPMC9845330 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature