Structure-Dependent Antimicrobial Theranostic Functions of Self-Assembled Short Peptide Nanoagents

Abstract

Gadolinium (Gd[III])-based nanoaggregates are potential noninvasive magnetic resonance imaging (MRI) probes with excellent spatial and temporal resolution for cancer diagnosis. Peptides conjugated with Gd can aid in supramolecular scaffolding for MRI nanoagents because of their inherent biocompatibility and degradability. We report here a strategy to tune the MR relaxivity of tumor cell-targeted nanoagents and enhance the antimicrobial and anticancer activities of nanoagents based on rationally designed antimicrobial peptide (AMP) assembly. A tripeptide with glycyl-l-histidyl-l-lysine (GHK) capable of Gd chelation was attached to short AMPs containing pyrazole amino acids that spontaneously assembled as a function of the number of hydrophobic amino acid residues and the peptide length of AMPs. Aqueous coassembly of GHK with tumor-targeting, cyclic arginine-glycine-aspartic acid (cRGD)-tagged AMPs resulted in the formation of micelles, fibrils, vesicles, sheets, and planar networks. Interestingly, the two-dimensional planar network nanostructure showed less antibacterial activity and tumor cell cytotoxicity but greater drug loading/delivery and magnetic resonance signaling than micelles because of its intrinsic structural characteristics. This study can provide a rational approach for the design and fabrication of clinically useful nanoagents.

Polycaprolactone-Based Mimetic Antimicrobial Peptide Copolymers Vesicles as an Effective Drug-Carrier for Cancer Therapy

“…This may be because the surface of the cancer cell membrane possesses more negative charges than normal cells [43]. Kim et al reported nanoparticles processing different cytotoxicity to cancer cells and normal cells [44]. They also reported that the interactions between the membrane and the vesicles were mainly affected by electrostatic and hydrophobic properties.…”

Systematic overview of soft materials as a novel frontier for MRI contrast agents

“…In 2017 Lee et al developed supramolecular theranostic nanoagents with antimicrobial activities. 50 These agents, based on the self-assembly of amphiphatic antimicrobial peptides (AMPs), are capable of Gd 3+ conjugation and tumor-targeting in aqueous solution. In detail, a series of AMPs (G1, G2, G3) consisting of N-alkyl/aryl pyrazole (Py) amino acids and arginine (Arg) building blocks were designed.…”

Covalently Conjugated Hydrogelators for Imaging and Therapeutic Applications

“…This agent spontaneously selfassembled into 2D-planar networks which showed improved drug loading/delivery, increased T 1 relaxivity of water protons, and magnetic resonance signaling. 27 Sun, Yang, and Chen et al used Gd 3+ to trigger the formation of self-assembling peptides naphthalene-GFFYGRGE (Nap-GFFYGRGE) and obtained an increased longitudinal relaxivity (r 1 ) value (58.9 mM −1 S −1 ). 28 In relation to the enhancement of MRI by Gd, Liang and coworkers discovered that, at a high magnetic field of 9.4 T, the T 2 -weighted MRI was enhanced after the self-assembly of the Gd(III)-chelating hydrogelators.…”