Structural Control of Self-assembled Peptide Nanostructures to Develop Peptide Vesicles for Photodynamic Therapy of Cancer

Vesicles such as liposomes, polymersomes, and exosomes have been widely used as drug delivery carriers; however, peptide vesicles (peptidesomes) despite their potential utility are far less well developed. Peptidesomes are distinctive because peptides play dual roles as a self-assembly building block and a bioactive functional unit. In order for peptidesomes to become successful nanodrugs, the issues related to differences in nanostructural properties between and conditions should be addressed. Here, we delineate a multivariate approach to feedback control the structures of peptide building blocks, nanoparticle size, drug loading process, nanoparticle aggregation, cytotoxicity, cell targeting capability, endosome disruption function, protease resistance, and performance, which eventually enabled the successful development of a highly efficacious peptidesome for cancer therapy. This study lays the groundwork for the successful translation of peptide nanodrugs.