Shape Effects of Peptide Amphiphile Micelles for Targeting Monocytes.

Johan Joo,Christopher Poon,Eun Chung,Sang Yoo

doi:10.3390/molecules23112786

Abstract

Peptide amphiphile micelles (PAMs) are a nanoparticle platform that have gained popularity for their targeting versatility in a wide range of disease models. An important aspect of micelle design is considering the type of hydrophobic moiety used to synthesize the PAM, which can act as a contributing factor regarding their morphology and targeting capabilities. To delineate and compare the characteristics of spherical and cylindrical micelles, we incorporated the monocyte-targeting chemokine, monocyte chemoattractant protein-1 (MCP-1), into our micelles (MCP-1 PAMs). We report that both shapes of nanoparticles were biocompatible with monocytes and enhanced the secondary structure of the MCP-1 peptide, thereby improving the ability of the micelles to mimic the native MCP-1 protein structure. As a result, both shapes of MCP-1 PAMs effectively targeted monocytes in an in vitro binding assay with murine monocytes. Interestingly, cylindrical PAMs showed a greater ability to attract monocytes compared to spherical PAMs in a chemotaxis assay. However, the surface area, the multivalent display of peptides, and the zeta potential of PAMs may also influence their biomimetic properties. Herein, we introduce variations in the methods of PAM synthesis and discuss the differences in PAM characteristics that can impact the recruitment of monocytes, a process associated with disease and cancer progression.

Highlights

In the past several decades, the development of peptide-based nanoparticles for applications in medicine have grown due to their targeting versatility, drug delivery potential, and diagnostic capabilities [1,2,3]
Molecules 2018, 23, 2786 their critical micelle concentration (CMC), Peptide amphiphiles (PAs) self-assemble into peptide amphiphile micelles (PAMs) partially through hydrophobic interactions that occur at the core of the micelle [4]
One advantage of inducing PA micellization is the enhancement of the secondary structure of the peptides via hydrogen bonding when incorporated within a PAM [1,2,12]

Summary

Introduction

In the past several decades, the development of peptide-based nanoparticles for applications in medicine have grown due to their targeting versatility, drug delivery potential, and diagnostic capabilities [1,2,3]. Peptide amphiphiles (PAs) are a class of molecules in which a peptide headgroup is conjugated to a hydrocarbon tail, resulting in structures that possess distinct hydrophobic and hydrophilic regions [9,10,11]. Molecules 2018, 23, 2786 their critical micelle concentration (CMC), PAs self-assemble into peptide amphiphile micelles (PAMs) partially through hydrophobic interactions that occur at the core of the micelle [4]. Synthetic peptides dispersed in solution lose much of their secondary structure, pairing the peptides with a lipid tail to form micelles can enhance the secondary structure that is characteristic of the endogenous peptide sequence within the full protein [2,12]

Methods

Discussion

Conclusion