Engineering a protein-based nanoplatform as an antibacterial agent for light activated dual-modal photothermal and photodynamic therapy of infection in both the NIR I and II windows

• Published in: Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2018-02, Vol.6 (5), p.732-739
• Main Authors: Gao, D Y, Ji, X, Wang, J L, Wang, Y T, Li, D L, Liu, Y B, Chang, K W, Qu, J L, Zheng, J, Yuan, Z
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Bacteria; Bactericidal activity; Blood vessels; Conjugation; Copper sulfides; Drug resistance; E coli; Health risks; I.R. radiation; Infections; Irradiation; Lasers; Multidrug resistance; Nanoparticles; Near infrared radiation; Photodynamic therapy; Protein engineering; Proteins; Public health; Radiation; Reactive oxygen species; Sulfide; Thermal energy
• ISSN: 2050-750X; 2050-7518
• DOI: 10.1039/c7tb02990j

The rapid rise of drug- and multi-drug resistant pathogenic bacteria constitutes an increasing risk to global public health. Thus, it is essential to develop new agents and/or strategies to overcome the antibiotic resistance crisis. Herein, ultra-small protein-based nanoparticles (NPs) with absorption covering both the near-infrared (NIR) I and II windows were constructed as novel antibacterial agents, which introduced a killing strategy utilizing the synergistic photothermal and photodynamic effects. The agent engineered by the conjugation of Ce6 molecules to ultra-small hydrophilic protein-modified copper sulfide NPs can transfer light energy into thermal energy for photothermal therapy and produce reactive oxygen species for photodynamic therapy. Under the irradiation of both NIR I and II lasers, the agent demonstrated a potent bacteria killing activity on both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) in vitro bacteria with high efficacy and safety. Furthermore, the as-prepared NPs also displayed an efficient in vivo bactericidal activity in a mouse model as monitored by measuring the photoacoustic signals of the blood vessels around the infection site. Consequently, leveraging the synergistic photothermal and photodynamic effects, the as-designed ultra-small NIR NPs may eliminate the emergence of drug resistance due to the mechanical destruction of the bacteria cell, thus representing a promising approach to control the antibiotic resistance crisis.