Oxygen Self-Supplying Nanotherapeutic for Mitigation of Tissue Hypoxia and Enhanced Photodynamic Therapy of Bacterial Keratitis

Abstract

Hypoxia, a common characteristic of bacterial infections, is known to be closely associated with the emergence of multidrug-resistant bacteria, which hastens the need to develop advanced microbicides and antibacterial techniques. Photodynamic therapy is a promising strategy to reduce bacterial antibiotic resistance and employs photosensitizers, excitation light sources, and sufficient oxygen to generate toxic reactive oxygen species (ROS). The inherent limitation of PDT is that the generation of ROS is restricted by the hypoxic microenvironment in infection sites. Here, an oxygen self-supplying nanotherapeutic is developed to enhance antibacterial activity against multidrug-resistant bacteria on the basis of fluorinated boron dipyrromethene (BODIPY)-based glycomimetics. The nanotherapeutic not only could capture the bacteria efficiently but also was able to act as an oxygen carrier to relieve the hypoxic microenvironment of bacterial infections, thus achieving enhanced PDT efficacy. In a Pseudomonas aeruginosa infection of a rat cornea, typical administration of the nanotherapeutic decreased the infiltrate and showed a faster healing capacity in comparison with BODIPY-based glycomimetics. Self-supplying oxygen nanotherapeutics that relieve the hypoxic microenvironment and interfere with bacterial colonization have been shown to be a promising candidate for the management of drug-resistant microbial keratitis.

Virus-like-inspired nanoparticles facilitate bacterial internalization for enhanced eradication of drug-resistant pathogens

“…EB was used to locate dead bacteria in the biofilm and exhibited red fluorescence; FITC-ConA was used as a probe to determine extracellular polysaccharides and exhibited green florescence. 44 As shown in Fig. 8A, without NIR laser irradiation, the biofilm was dense and formed as a whole, similar to the structure of the original biofilm in the dark without FWAPNP treatment.…”

Photodynamic disinfection and its role in controlling infectious diseases

“…In this regard, some strategies have been proposed to reduce biofilm hypoxia, such as hyperbaric oxygen therapy [ 126 ], the use of MnO 2 nanosheets which catalyze O 2 formation from H 2 O 2 [ 127 ] or O 2 -carrying perfluorohexane-loaded liposomes [ 128 ]. In particular, this last approach has recently been successfully employed in the treatment of bacterial keratitis in rat cornea [ 129 ].

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Selenophene-Modified Boron Dipyrromethene-Based Photosensitizers Exhibit Photodynamic Inhibition on a Broad Range of Bacteria

“… 31 An oxygen self-supplying BODIPY compound was demonstrated to inhibit P. aeruginosa by relieving hypoxia to boost the PDT effect. 32 A neutral BODIPY derivative was demonstrated to kill S. aureus , P. aeruginosa , and C. albicans among 15 BODIPY compounds. 33 In our previous work, we reported the mitochondria targeting BODIPY-based PDT drugs inducible in the near-infrared (NIR) range and they efficiently kill cancer cells even under hypoxic conditions.…”

“…An oxygen self-supplying BODIPY compound was demonstrated to inhibit P. aeruginosa by relieving hypoxia to boost the PDT effect . A neutral BODIPY derivative was demonstrated to kill S.…”