3 years ago

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

Structure-Dependent Antimicrobial Theranostic Functions of Self-Assembled Short Peptide Nanoagents
Jeong-Kyu Bang, Eun Hee Han, Woo-Young Bang, MiJa Ahn, Inhye Kim, Eunji Lee, Eunhee Ko, Seon-Mi Jin
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 Gd3+ 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 Gd3+ 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.

Publisher URL: http://dx.doi.org/10.1021/acs.biomac.7b00951

DOI: 10.1021/acs.biomac.7b00951

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