Hierarchically Multivalent Peptide–Nanoparticle Architectures: A Systematic Approach to Engineer Surface Adhesion

Abstract

The multivalent binding effect has been the subject of extensive studies to modulate adhesion behaviors of various biological and engineered systems. However, precise control over the strong avidity-based binding remains a significant challenge. Here, a set of engineering strategies are developed and tested to systematically enhance the multivalent binding of peptides in a stepwise manner. Poly(amidoamine) (PAMAM) dendrimers are employed to increase local peptide densities on a substrate, resulting in hierarchically multivalent architectures (HMAs) that display multivalent dendrimer-peptide conjugates (DPCs) with various configurations. To control binding behaviors, effects of the three major components of the HMAs are investigated: i) poly(ethylene glycol) (PEG) linkers as spacers between conjugated peptides; ii) multiple peptides on the DPCs; and iii) various surface arrangements of HMAs (i.e., a mixture of DPCs each containing different peptides vs DPCs cofunctionalized with multiple peptides). The optimized HMA configuration enables significantly enhanced target cell binding with high selectivity compared to the control surfaces directly conjugated with peptides. The engineering approaches presented herein can be applied individually or in combination, providing guidelines for the effective utilization of biomolecular multivalent interactions using DPC-based HMAs.

Cytochalasin B Treatment and Osmotic Pressure Enhance the Production of Extracellular Vesicles (EVs) with Improved Drug Loading Capacity

“…We then examined the drug loading efficiencies of the produced EVs and investigated the correlation with the amount of intravesicular protein. Generation 7 (G7) polyamidoamine (PAMAM) dendrimers were employed as a model drug due to their high degree of chemical versatility for manipulating the surface charge density [ 45 , 46 , 47 , 48 ]. Three types of G7 dendrimers, having either positive (G7-NH 2 ), neutral (G7-Ac), or negative (G7-COOH) charges were prepared using our previously developed protocols.…”

Dendrimer-Peptide Conjugates for Effective Blockade of the Interactions between SARS-CoV-2 Spike Protein and Human ACE2 Receptor

“…Although our study was focused on blocking the interactions between SARS-CoV-2 Spike protein and ACE2 proteins, our DPC systems can be further employed for inhibiting other receptors that may cause the entry of SARS-CoV-2 into cells. Previously, our team has shown that the dendrimer-mediated multivalent binding effect can facilitate the targeting of multiple proteins on the cell surface by co-conjugating peptides that target different cell surface proteins on the dendrimer surface . Thus, other types of peptides that inhibit the entry of virus to the cells may be coimmobilized on our DPC system, which has potential to further prevent the SARS-CoV-2 infection.…”

“…Previously, our team has shown that the dendrimer-mediated multivalent binding effect can facilitate the targeting of multiple proteins on the cell surface by co-conjugating peptides that target different cell surface proteins on the dendrimer surface. 37 Thus, other types of peptides that inhibit the entry of virus to the cells may be coimmobilized on our DPC system, which has potential to further prevent the SARS-CoV-2 infection. The therapeutic efficacy, bioavailability, and pharmacokinetics of our inhibitor will be the subject of our future studies that will focus on their in vivo behaviors.…”

“…Herein, we examined the use of engineered dendrimer-peptide conjugates (DPCs) for COVID-19 treatment. Previously, DPCs have demonstrated potent protein–protein interaction (PPI) inhibitory functions, high target affinity and selectivity, and enhanced bioavailability or pharmacokinetics compared to the free peptides. − Considering that S proteins form trimers and bind to ACE2 protein via multivalent binding, the utilization of DPCs for COVID-19 treatment is a promising strategy to develop strong inhibitors of S protein binding to ACE2 receptors. In this study, two peptide fragments of ACE2 were incorporated into a single sequence and conjugated to the surface of poly­(amidoamine) (PAMAM) dendrimers, based on the assumption that the multivalent ACE2-mimicking peptides could effectively block the S protein–ACE2 interaction (Figure ).…”

Cost-Effective Bull’s Eye Aperture-Style Multi-Band Metamaterial Absorber at Sub-THz Band: Design, Numerical Analysis, and Physical Interpretation

“…Imaging with THz radiation is appealing for security [44][45][46] and biomedical applications [47][48][49][50][51] due to its ability to penetrate most dry and nonpolar materials without harming the body cells [49]. There have been lots of reports on the excitation of surface plasmon resonances and magnetic plasmon resonances in metamaterial and metasurface designs in optical sensing applications [52][53][54][55][56][57]. Therefore, functional devices in the THz band have also become one of the recent research hotspots [37,[58][59][60][61].…”