Infection Microenvironment-Responsive Multifunctional Peptide Coated Gold Nanorods For Bimodal Antibacterial Applications

The abuse of antibiotics has led to bacterial drug resistance, which hinders traditional treatments for infection. It is a vitally important task to develop new methods for combating bacterial infection. In this work, we design a multifunctional peptide (BrEK) that consists of three functional building blocks: an antimicrobial sequence (BF2b), a gelatinase B responsive linker, and a zwitterionic antifouling block. The BrEK peptide is conjugated onto gold nanorods (AuNRs) via a cysteine on one end of the peptide sequence, with excellent photothermal conversion ability under near-infrared (NIR) light. The obtained AuNR@BrEK are tested in vitro and in vivo for antibiotic capacity against methicillin-resistant Staphylococcus aureus (MRSA). The multifunctional peptide coating provides the nanocomposite excellent biocompatibility, relative long circulation in blood, infection microenvironment responsive targeting ability, and unique antibacterial performance. Ultimately, we aim to eliminate drug resistance bacteria by (1) integrating infection microenvironment responsiveness for efficient targeting, (2) capitalizing on antibacterial capacity of BF2b peptides, and (3) developing photothermal sterilization. Transmittance electron microscopy, dynamic light scatter, and zeta potential measurements are introduced to characterize the synthesis of AuNR@BrEK. The evaluation of particle stability is conducted by Fouriertransform infrared spectroscopy and UV?vis spectroscopy. Photothermal conversion capacity of AuNR@BrEK is examined via photothermal effect measurement. Cell viability and hemolysis assay are conducted to further assess the biocompatibility of AuNR@BrEK (200 mu g/mL). Lastly, results from the in vitro and in vivo experiments indicate the outstanding antibacterial activity of AuNR@BrEK (10 mg/kg). Such multifunctional gold nanorods represent an important step forward in the goal to combat bacterial resistance.