Multifunctional Antimicrobial Biometallohydrogels Based on Amino Acid Coordinated Self-Assembly.

Jingwen Song,Tifeng Jiao,Xuehai Yan,Chengqian Yuan,Ruirui Xing,Mengyao Yang,Dave J Adams

doi:10.1002/smll.201907309

Abstract

There is a real need for new antibiotics against self-evolving bacteria. One option is to use biofriendly broad-spectrum and mechanically tunable antimicrobial hydrogels that can combat multidrug-resistant microbes. Whilst appealing, there are currently limited options. Herein, broad-spectrum antimicrobial biometallohydrogels based on the self-assembly and local mineralization of Ag+ -coordinated Fmoc-amino acids are reported. Such biometallohydrogels have the advantages of localized delivery and sustained release, reduced drug dosage and toxicity yet improved bioavailability, prolonged drug effect, and tunable mechanical strength. Furthermore, they can directly interact with the cell walls and membrane, resulting in the detachment of the plasma membrane and leakage of the cytoplasm. This leads to cell death, triggering a significant antibacterial effect against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria in cells and mice. This study paves the way for developing a multifunctional integration platform based on simple biomolecules coordinated self-assembly toward a broad range of biomedical applications.

Highlights

There is a real need for new antibiotics against self-evolving bacteria
In situ mineralization of AgNPs ensures the controlled spatial distribution of AgNPs in the hydrogel matrix, which is of key importance for sustainable release of Ag+, improved antimicrobial efficacy and tunable mechanical properties.[14,15a] It has been reported that several N-(fluorenyl-9-methoxycarbonyl) (Fmoc)-modified amino acids possess inherent antimicrobial activities and good biocompatibility.[9a,11b,14] By screening Fmoc-amino acids (Figure S1, Supporting Information), we found four can form metallohydrogels based on the coordination interaction between Fmoc-amino acids and Ag+ in addition to the multiple noncovalent interactions between Fmoc-amino acids
We have demonstrated a simple yet versatile strategy for formation of effective and broad-spectrum antimicrobial biometallohydrogels based on Ag+-coordinated Fmocamino acids self-assembly and local mineralization

Summary

Results and Discussion

Our Fmoc-amino acid metallohydrogels are fabricated through amino acid coordinated self-assembly with Ag+. The metallohydrogels have lower minimum inhibitory concentrations (around 0.4 × 10−3 m Ag and 0.2 mg mL−1 Fmoc-amino acids) against both E. coli and S. aureus compared to the individual Ag+ and Fmoc-amino acid solution (Figures S12 and S13, Supporting Information) This can be ascribed to the synergistic antimicrobial effect of Fmoc-amino acids and AgNPs against bacterial growth, leading to a relative lower OD value compared to the control experiment after 48 h. No obvious inflammation and size difference of wound are observed on the groups treated by Fmoc-amino acid metallohydrogels and SSD, while slight infection emerged from the control group after 4-day treatment (Figure S16, Supporting Information). It is noteworthy to mention that Fmoc-Leu hydrogels reduce the size of the wounds more effectively than other amino acids after treatment for 12 days (Figure 4a) This result is consistent with the in vitro testing, which showed that the Fmoc-Leu metallohydrogels were more effective at inhibiting E. coli and S. aureus. All the histological results indicate that the Fmoc-amino acids metallohydrogels can accelerate the tissue regeneration in the wound healing

Conclusion

Experimental Section

Conflict of Interest