Abstract
With the merits of excellent efficacy, safety, and facile implementation, antibacterial photodynamic therapy (APDT) represents a promising means for treating bacterial infections. However, APDT shows an unsatisfactory efficacy in combating antibiotic-resistant Gram-negative bacteria due to their specific cell wall structure. In this work, we report a perfluorocarbon nanoemulsion (Ce6@FDC) used as a multifunctional nanocargo of photosensitizer and oxygen for sensitizing antibiotic-resistant Gram-negative bacteria to APDT. Ce6@FDC was fabricated via ultrasonic emulsification with good colloidal stability, efficient Ce6 and oxygen delivery, and excellent photodynamic activity. Meanwhile, Ce6@FDC could strongly bind with Gram-negative Acinetobacter baumannii (A. baumannii) and Escherichia coli (E. coli) via electrostatic interaction, thus leading to notable photodynamic bactericidal potency upon irradiation. In addition, oxygenated Ce6@FDC also exhibited a remarkable efficacy in eradicating Gram-negative bacteria biofilm, averaging five log units lower than the Ce6 group under identical conditions. Taken together, we demonstrate that photodynamic perfluorocarbon nanoemulsion with oxygen-delivery ability could effectively kill planktonic bacteria and remove biofilm, representing a novel strategy in fighting against antibiotic-resistant Gram-negative bacteria.
Highlights
Academic Editor: Fu-Gen WuAntibiotics play an important role in the treatment of various pathogenic microbial infections
Due to the abuse of antibiotics, the spread of antibiotic-resistant bacterial strains has arisen as one of the most worrying threats to public health in recent years, such as E. coli, Staphylococcus aureus, Pseudomonas aeruginosa, and A. baumannii, etc. [1,2,3]. These antibiotic-resistant bacteria could invalidate the primary treatment of traditional antibiotics through precise mutations, efflux pump expression, or up-regulation of defense-associated enzymes, and so on [4,5]
Inspired by the success of the oxygen-delivery strategy for the empowering of antibiotics and antibacterial photodynamic therapy (APDT) [16,25], in this work, we propose an oxygen-affordable photodynamic nanomedicine for the sensitizing of Gram-negative bacteria to APDT, especially clinically related drug-resistant strains (Figure 1)
Summary
Antibiotics play an important role in the treatment of various pathogenic microbial infections. The sensitivity of Gram-negative bacteria to PDT can be immensely improved via supplementing oxygen during the photodynamic process and relieving the anoxic or hypoxic environment. PFCs might be preferable for the sensitizing of antibiotic-resistant Gram-negative bacteria to conventional APDT. Inspired by the success of the oxygen-delivery strategy for the empowering of antibiotics and APDT [16,25], in this work, we propose an oxygen-affordable photodynamic nanomedicine (denoted Ce6@FDC) for the sensitizing of Gram-negative bacteria to APDT, especially clinically related drug-resistant strains (Figure 1). By designing a late-model oxygen-delivery system, the sensitivity of Gram-negative bacteria to APDT could be enhanced comprehensively, which provides a strategic reference for the development of new antimicrobial agents. Schematic illustration for the fabrication process of Ce6@FDC nanoemulsion and its oxygen gendelivery delivery for enhanced photodynamic antibacterial efficiency.
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