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

ABSTRACT: Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe₃O₄/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe₃O₄/CNT/Gent, is proven to efficiently target and eradicate MRSA-infected rabbit tibia osteomyelitis. Its robust antibacterial effectiveness is attributed to the precise bacteria-capturing ability and magnetic targeting of the nanocapturer, as well as the subsequent synergistic effects of precise microwaveocaloric therapy from Fe₃O₄/CNT and chemotherapy from the effective release of antibiotics in infection sites. The advanced target-nanocapturer of microwave-excited microwaveocaloric-chemotherapy with effective targeting developed in this study makes a major step forward in microwave therapy for deep tissue infections.

SUBMITTER: Qiao Y

PROVIDER: S-EPMC7477539 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Qiao Yuqian Y Liu Xiangmei X Li Bo B Han Yong Y Zheng Yufeng Y Yeung Kelvin Wai Kwok KWK Li Changyi C Cui Zhenduo Z Liang Yanqin Y Li Zhaoyang Z Zhu Shengli S Wang Xianbao X Wu Shuilin S

Nature communications 20200907 1

Owing to the poor penetration depth of light, phototherapy, including photothermal and photodynamic therapies, remains severely ineffective in treating deep tissue infections such as methicillin-resistant Staphylococcus aureus (MRSA)-infected osteomyelitis. Here, we report a microwave-excited antibacterial nanocapturer system for treating deep tissue infections that consists of microwave-responsive Fe3O4/CNT and the chemotherapy agent gentamicin (Gent). This system, Fe ...[more]

PMID: 32895387

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Project description:Intraperitoneal (IP) chemotherapy has revived hopes during the past few years for the management of peritoneal disseminations of digestive and gynecological cancers. Nevertheless, a poor drug penetration is one key drawback of IP chemotherapy since peritoneal neoplasms are notoriously resistant to drug penetration. Recent preclinical studies have focused on targeting the aberrant tumor microenvironment to improve intratumoral drug transport. However, tumor stroma targeting therapies have limited therapeutic windows and show variable outcomes across different cohort of patients. Therefore, the development of new strategies for improving the efficacy of IP chemotherapy is a certain need. In this work, we propose a new magnetically assisted strategy to elevate drug penetration into peritoneal tumor nodules and improve IP chemotherapy. A computational model was developed to assess the feasibility and predictability of the proposed active drug delivery method. The key tumor pathophysiology, including a spatially heterogeneous construct of leaky vasculature, nonfunctional lymphatics, and dense extracellular matrix (ECM), was reconstructed in silico. The transport of intraperitoneally injected magnetic nanoparticles (MNPs) inside tumors was simulated and compared with the transport of free cytotoxic agents. Our results on magnetically assisted delivery showed an order of magnitude increase in the final intratumoral concentration of drug-coated MNPs with respect to free cytotoxic agents. The intermediate MNPs with the radius range of 200-300 nm yield optimal magnetic drug targeting (MDT) performance in 5-10 mm tumors while the MDT performance remains essentially the same over a large particle radius range of 100-500 nm for a 1 mm radius small tumor. The success of MDT in larger tumors (5-10 mm in radius) was found to be markedly dependent on the choice of magnet strength and tumor-magnet distance while these two parameters were less of a concern in small tumors. We also validated in silico results against experimental results related to tumor interstitial hypertension, conventional IP chemoperfusion, and magnetically actuated movement of MNPs in excised tissue.

Dataset Information

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

Publications

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

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