Treatment of MRSA-infected osteomyelitis using bacterial capturing, magnetically targeted composites with microwave-assisted bacterial killing

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Osteomyelitis is an inflammatory bone disease caused by infection microorganisms which leads to progressive bone destruction and loss1. If uncontrolled, it might lead to lifelong disability, or cause life-threatening sepsis2. Clinically, osteomyelitis is often treated by systemically injecting a large amount of antibiotics with a long treatment and recovery time3. The overuse of antibiotics not only leads to drug-resistance in clinic, but also causes serious adverse reactions4,5. Meanwhile, most of the emerging antibacterial strategies such as phototherapy is noneffective owing to the poor penetration depth of near infrared light.

 

In our most recent study in Nature Communications, our team present a possible solution for such deep tissue infection. We first choose microwaves (MV), which has deeper penetration ability than light, as the external stimulus source. Then we design a microwave responsive agent Fe3O4/CNT, which can not only respond to external microwaves to generate microwaveocaloric, but also target and capture bacteria through the oxygen-containing functional groups on the CNT. To minimize the adverse effects of hyperthermia induced by MV, an effective strategy of eradicating deep tissue infection is to combine microwaveocaloric therapy (MCT) with chemotherapy. Therefore, we load gentamicin (Gent) on the microwave responsive agent and use the phase change material, which can change between solid and liquid after temperature stimulation, to control the release of the drug.

 

Caption

Fig. 1 The schematic illustration of the microwaveocaloric-chemotherapy (MCCT) of Fe3O4/CNT/Gent. MRSA: Methicillin-resistant Staphylococcus aureus. Source file: https://www.nature.com/articles/s41467-020-18268-0

Fe3O4/CNT/Gent (nanocapturer) with good biocompatibility exhibited potent microwaveocaloric-chemo-therapy antibacterial performance against MRSA (99.556±0.427%) and Escherichia coli (98.529±0.404%) in a short time (20 minutes). We proposed the mechanism underlying the bactericidal action of nanocapturer (Fig. 1). First, the nanocapturer captured the bacteria through anchoring with amino groups on bacteria and applied the magnetic field to prevent the captured MRSA from spreading with the blood, avoiding sepsis and organ infections. Then the microwaveocaloric effect of the nanocapturer will effectively damage the bacterial membrane while the phase change material melts to release the Gent.

The target-guided MCCT in one individual microwavesensitizer, which achieves ordered and multiple targeting simply by varying the external conditions. This nanocapturer reveals new design principles for the implementation of efficient microwavesensitizer in clinical applications.

 Link: https://www.nature.com/articles/s41467-020-18268-0

References

  1. Shi M, et al. Dual functional monocytes modulate bactericidal and anti-inflammation process for severe osteomyelitis treatment. Small 16, 1905185 (2020).
  2. Brummerstedt M, Bangstrup M, Barfod TS. High mortality from pyogenic vertebral osteomyelitis: a retrospective cohort study. Spinal Cord Ser. Cases 4, 59 (2018).
  3. Li H-K, et al. Oral versus intravenous antibiotics for bone and joint infection. Engl. J. Med. 380, 425-436 (2019).
  4. Baker S, Thomson N, Weill F-X, Holt KE. Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens. Science 360, 733 (2018).
  5. Hussain S, et al. Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy. Biomed. Eng. 2, 95-103 (2018).

shuilin

Professor, Tianjin University

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