Allosteric targeted drug delivery for enhanced blood-brain barrier penetration via mimicking transmembrane domain interactions.

ABSTRACT: Current strategies for active targeting in the brain are entirely based on the effective interaction of the ligand with the orthosteric sites of specific receptors on the blood-brain barrier (BBB), which is highly susceptible to various pathophysiological factors and limits the efficacy of drug delivery. Here, we propose an allosteric targeted drug delivery strategy that targets classical BBB transmembrane receptors by designing peptide ligands that specifically bind to their transmembrane domains. This strategy prevents competitive interference from endogenous ligands and antibodies by using the insulin receptor and integrin α_v as model targets, respectively, and can effectively overcome pseudotargets or target loss caused by shedding or mutating the extracellular domain of tar

SUBMITTER: Tang K 

PROVIDER: S-EPMC11986143 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature