Targeting senescent cells, particularly senescent vascular smooth muscle cells (VSMCs), is an important phase in treating age-related and vascular diseases. Research shows that programmed death-ligand 1 (PD-L1) expression is increased in senescent cells both in vitro and in vivo.
Our researchers developed extracellular vesicles (EVs) or lipid-based nanoparticles with a PDL-1 binding peptide to efficiently deliver gene-based therapeutics, protein or drug to senescent cells in vivo. Preliminary findings show better uptake of modified EVs in senescent VSMCs, both in vitro and in vivo. Future studies will focus on engineering human contractile vascular smooth cells derived extrasellar vesicles via the approach to target the senescent vascular smooth cells in vivo either during aging or vascular diseases. Modifications to lipid-based nanoparticles can be employed in a similar manner to target senescent cells.
Modification of the surface of EVs with PD-L1 binding peptide (PD-L1-BP) by hydrophobic insertion using DMPE-PEG for targeting delivery of senescent VSMCs.
In vivo delivery of Cy5.5-PD-L1-BP-EVs (50 µg) in aged female mice showed better uptake in aorta compared with Cy5.5-PEG-EVs.