Novel nanoreactor CU@G - AMPs: A promising solution for antibacterial therapy

In a latest research reported in Engineering researchers from Fuzhou University and Hunan Agricultural University have developed an innovative artificial complex, Cu@G-AMPs, which shows great potential in antibacterial therapy, especially against drug-resistant bacteria like methicillin-resistant Staphylococcus aureus (MRSA).

The development of Cu@G-AMPs is inspired by natural host defense mechanisms. Antimicrobial peptides (AMPs) are considered ideal alternatives to traditional antibiotics due to their unique antibacterial activity. The amino-terminal copper-nickel binding motif (ATCUN) in AMPs plays a crucial role in immune regulation. Leveraging this, the researchers incorporated single-atom Cu catalysts into an ATCUN - motif AMP complex, creating Cu@G - AMPs.

The preparation of Cu@G-AMPs involves a multi - step process. First, single Cu atoms were anchored to a guanine-derived sheet substrate through coordination pyrolysis, forming Cu@G. Then, ATCUN - motif AMPs were modified onto Cu@G via an amide reaction to obtain Cu@G-AMPs.

The characterization of Cu@G - AMPs was carried out using various advanced techniques. High - angle annular dark-field scanning transmission electron microscopy (HAADF - STEM) revealed highly dispersed single Cu atoms in the complex. Multiple molecular-structure-identification techniques such as Fourier-transform infrared spectroscopy (FTIR), Zeta potential tests, and X-ray diffraction (XRD) further confirmed the successful formation of Cu@G-AMPs, an antibiotic-free nanomaterial.

The antibacterial properties of Cu@G-AMPs were thoroughly investigated. In vitro experiments showed that it exhibited antibacterial activity against MRSA, especially under acidic conditions, which is consistent with the Fenton-like reaction mechanism. The complex generated reactive oxygen species (ROS) from H₂O₂, and as the concentration of Cu@G-AMPs increased, so did the amount of ROS. The toxicity tests indicated that Cu@G-AMPs had low cytotoxicity to MC3T3-E1 cells and did not cause red blood cell lysis within the antibacterial concentration range, demonstrating its ideal biocompatibility.

The study also explored the bacteriostatic mechanisms of Cu@G - AMPs. Proteomics analysis revealed that it disrupted the stress response systems of MRSA, including quorum sensing regulation, antioxidant enzymes, and gene repair and recombination.

Moreover, the in vivo performance of Cu@G-AMPs was evaluated using a mouse wound - resistant bacterial infection model. The results showed that Cu@G-AMPs effectively promoted wound healing. It pulled edge closure, stabilized granulation tissue, promoted collagen fiber proliferation, alleviated inflammation, and promoted neovascularization in wound areas infected by MRSA.

This research on Cu@G-AMPs provides a new perspective on addressing the global challenge of antibiotic resistance. As drug-resistant bacteria continue to threaten public health, the development of such novel antibacterial agents could pave the way for more effective and sustainable antibacterial therapies in the future.

The paper “Incorporating Single-Copper Sites and Host Defense Peptides into a Nanoreactor for Antibacterial Therapy by Bioinspired Design,” authored by Xuan Chen, Wei Luo, Qun Gao, Congrong Chen, Lichan Li, Dongbo Liu, Shaoyun Wang. Full text of the open access paper: https://doi.org/10.1016/j.eng.2024.09.021. For more information about the Engineering, follow us on X (https://twitter.com/EngineeringJrnl) & like us on Facebook (https://www.facebook.com/EngineeringJrnl).