Multivalent effect of peptide functionalized polymeric nanoparticles towards selective prostate cancer targeting. Issue 5 (8th February 2023)

• Record Type: Journal Article
• Authors: Murar, Madhura; Pujals, Silvia; Albertazzi, Lorenzo
• Is Part Of: Nanoscale advances. Volume 5:Issue 5(2023)
• Page Start: 1378
• Page End: 1385
• Publication Date: 2023-02-08
• Subjects: 620.5
• DOI: 10.1039/d2na00601d
• Languages: English
• ISSNs: 2516-0230

Abstract

Abstract : Multivalent nanoparticles facilitate simultaneous interaction of weak surface ligands with multiple target receptors resulting in higher avidity and enhanced cell selectivity. Abstract : The concept of selective tumor targeting using nanomedicines has been around for decades; however, no targeted nanoparticle has yet reached the clinic. A key bottleneck is the non-selectivity of targeted nanomedicines in vivo, which is attributed to the lack of characterization of their surface properties, especially the ligand number, thereby calling for robust techniques that allow quantifiable outcomes for an optimal design. Multivalent interactions comprise multiple copies of ligands attached to scaffolds, allowing simultaneous binding to receptors, and they play an important role in targeting. As such, 'multivalent' nanoparticles facilitate simultaneous interaction of weak surface ligands with multiple target receptors resulting in higher avidity and enhanced cell selectivity. Therefore, the study of weak binding ligands for membrane-exposed biomarkers is crucial for the successful development of targeted nanomedicines. Here we carried out a study of a cell targeting peptide known as WQP having weak binding affinity for prostate specific membrane antigen, a known prostate cancer biomarker. We evaluated the effect of its multivalent targeting using polymeric NPs over its monomeric form on the cellular uptake in different prostate cancer cell lines. We developed a method of specific enzymatic digestion to quantify the number of WQPs on NPs having different surface valencies and observed that increasing valencies resulted in a higher cellular uptake of WQP-NPs over the peptide alone. We also found that WQP-NPs showed higher uptake in PSMA over-expressing cells, attributed to a stronger avidity for selective PSMA targeting. This kind of strategy can be useful for improving the binding affinity of a weak ligand as a means for selective tumor targeting.