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.

中文翻译：

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自组装短肽纳米剂的结构依赖性抗菌治疗功能

基于d（Gd [III]）的纳米聚集体是潜在的无创磁共振成像（MRI）探针，具有出色的时空分辨率，可用于癌症诊断。与Gd ³⁺缀合的肽由于其固有的生物相容性和可降解性，因此可以辅助MRI纳米剂的超分子支架。我们在这里报告了一种战略，以调整针对肿瘤细胞的纳米剂的MR弛豫性，并基于合理设计的抗菌肽（AMP）组件增强纳米剂的抗微生物和抗癌活性。具有Gd ^3+的糖基-1-组氨酸-1-赖氨酸（GHK）的三肽螯合剂连接到含有吡唑氨基酸的短AMPs上，这些AMPs根据疏水性氨基酸残基的数量和AMPs的肽长度自发组装。GHK与靶向肿瘤的，带有环状精氨酸-甘氨酸-天冬氨酸（cRGD）标记的AMP的水共组装导致胶束，原纤维，囊泡，薄片和平面网络的形成。有趣的是，由于其固有的结构特征，二维平面网络纳米结构显示出比胶束更少的抗菌活性和肿瘤细胞的细胞毒性，但更大的载药量/传递和磁共振信号传递。这项研究可以为临床上有用的纳米剂的设计和制造提供一种合理的方法。