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

다국어 초록 (Multilingual Abstract)

<P>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<SUP>3+</SUP> 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-<SMALL>l</SMALL>-histidyl-<SMALL>l</SMALL>-lysine (GHK) capable of Gd<SUP>3+</SUP> 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.</P><P><B>Graphic Abstract</B>
<IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2017/bomaf6.2017.18.issue-11/acs.biomac.7b00951/production/images/medium/bm-2017-00951h_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bm7b00951'>ACS Electronic Supporting Info</A></P>