Multivalent effect of peptide functionalized polymeric nanoparticles towards selective prostate cancer targeting

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Selective tumor targeting with nanomedicines is a long-standing goal, yet clinical translation is limited by poor in vivo selectivity.
• Nanoparticle surface properties, particularly ligand density, are critical for effective targeting but often lack thorough characterization.
• Multivalent interactions, where multiple ligands bind simultaneously, enhance avidity and cell selectivity, crucial for weak-affinity ligands.

Purpose of the Study:

• To investigate the impact of multivalent targeting using a weak-affinity peptide (WQP) on polymeric nanoparticles (NPs) for prostate cancer cell lines.
• To develop a method for quantifying ligand density on nanoparticles to optimize nanomedicine design.
• To evaluate the enhanced cellular uptake and selective targeting of WQP-functionalized NPs against prostate specific membrane antigen (PSMA).

Main Methods:

• Development of polymeric nanoparticles (NPs) functionalized with varying densities of the WQP peptide.
• Establishment of a specific enzymatic digestion method to accurately quantify WQP density on the NP surface.
• In vitro evaluation of cellular uptake in different prostate cancer cell lines with varying PSMA expression levels.

Main Results:

• Increasing WQP valency on NPs significantly enhanced cellular uptake compared to the monomeric peptide.
• WQP-NPs demonstrated higher uptake in PSMA-overexpressing prostate cancer cells, indicating improved avidity and selective targeting.
• Quantifiable characterization of NP surface ligand density was achieved, enabling optimization of nanomedicine design.

Conclusions:

• Multivalent display of weak-affinity ligands like WQP can overcome limitations in targeting efficiency for nanomedicines.
• This strategy enhances binding avidity, leading to improved selectivity for cancer biomarkers such as PSMA.
• The developed method for quantifying ligand density is vital for the rational design of targeted nanomedicines.