A research team from the Fujian Institute of Research on the Structure of Matter (FJIRSM) of the Chinese Academy of Sciences (CAS), led by Prof. Chen Xueyuan, achieved noninvasive phototheranostics in a mouse model with Pseudomonas aeruginosa biofilm-induced pulmonary infection, according to a study published in ACS Nano.
Schematic representation of noninvasive theranostic Aly-NaNdF4 nanohybrids against P. aeruginosa biofilm induced pulmonary infection. Image Credit: Prof. Chen’s Group, Chinese Academy of Sciences
Bacterial biofilm infections are one of the main causes of morbidity and mortality for patients with cystic fibrosis or compromised immune systems. The standard course of treatment for biofilm infections is rigorous antibiotic therapy. Carefully crafted agents are desperately needed for in vivo diagnosis and accurate anti-biofilm therapy without bacterial resistance. Regretfully, no efficient agent has yet been created to complete these tasks.
Through an enrichment-encapsulating approach, researchers created novel sunflower-like structured alginate lyase (Aly)-NaNdF4 nanohybrids that demonstrated a second near-infrared (NIR-II) luminescence emission, an excellent photothermal conversion efficiency, and the perfect particle size for lung delivery.
When Aly-NaNdF4 nanohybrids were placed in biofilm-infected lungs, targeted biofilm degradation occurred because the acidic environment caused pH-responsive Aly molecules to be released from the nanohybrids' mesopores. The nanohybrids also displayed a significant positive charge, which improved their adherence to bacteria and increased their stay in the lung.
The degree of infection and efficacy of treatment could be assessed through real-time monitoring of the luminescence intensity of the nanohybrids in the lungs.
Researchers demonstrated that the nanohybrids could achieve strong biofilm eradication by combining the synergistic effects of Aly and photothermal therapy. P. aeruginosa's in vitro viability was lowered by 5.3 log10, which had a disinfecting effect. Around 94% of the bacteria in the treated mice's lungs were removed.
Notably, the nanohybrids could be eliminated from the body on day eight after an intravenous injection, thereby avoiding the possible long-term toxicity of nanomaterials. They were primarily metabolized in the liver and spleen.
This study explored the potential of biofilm-targeted theranostic nano agents based on luminescent lanthanide nanohybrids to treat internal organ infections. It will benefit precision medicine research and clinical practice regarding the management of biofilm-associated infections.
Journal Reference:
Li, Z., et al. (2024) Customized Lanthanide Nanobiohybrids for Noninvasive Precise Phototheranostics of Pulmonary Biofilm Infection. ACS Nano. doi.org/10.1021/acsnano.4c00777