Synergistic chemotherapy, physiotherapy and photothermal therapy against bacterial and biofilms infections through construction of chiral glutamic acid functionalized gold nanobipyramids

Sepsis and implant-related bacterial infections are mainly caused by Gram-positive bacteria accompanied with the notorious drug resistance and biofilms formation. Although the recently concerned photothermal therapy (PTT) shows good performance in killing of planktonic bacteria and removal of biofilms, the issue of potential thermal damage to normal tissue is urgent to be solved due to the non-targeting to bacteria. Here, we constructed a chiral glutamic acid functionalized gold nanobipyramids (Au NBPs) for enhanced PTT against bacterial and biofilms infections based on both chemical and physical interactions with bacteria. Specifically, the conjugation of d/l-glutamic acid (d/l-Glu) obviously enhanced the targeting and interactions of Au NBPs with bacterial cell wall leading to the biological restriction of nucleic acids. While the sharp tips and small size of Au NBPs enabled the penetration into bacterial cell wall and biofilms for cicada's wings bionic damage to bacterial cell wall and leakage of components. Furthermore, antibacterial mechanism examination confirmed the chemical and physical effects of d/l-Glu and nanobipyramids structure leading to the considerable DNA and nucleic acids leakage, which was greatly enhanced during PTT treatment. Both in vitro and in vivo antibacterial and anti-biofilms measurements verified high efficiency in killing of bacteria and eliminating of biofilms through a synergistic chemotherapy, physiotherapy and PTT functions. Furthermore, the quick targeting of chiral Au NBPs to the bacteria and penetrating into extracellular matrix effectively avoided the nonspecific damage to normal cells. Therefore, this work provides a novel strategy to combat bacterial and biofilms infections in a more smart way owing to the chiral amino acid modification and synergistic antibacterial effects.