A novel synergistic enzyme-antibiotic therapy with immobilization of mycobacteriophage Lysin B enzyme onto Rif@UiO-66 nanocomposite for enhanced inhaled anti-TB therapy; Nanoenzybiotics approach

• Published in: International journal of biological macromolecules 2024-03, Vol.262, p.129675-129675, Article 129675
• Main Authors: Eldin, Zienab E., Dishisha, Tarek, Sayed, Ossama M., Salama, Hanaa M., Farghali, Ahmed
• Format: Article
• Language: English
• Subjects: Biodistribution; Cytotoxicity; Enzyme-antibiotic combination; Metal-organic framework; Mycobacteriophage D29 Lysin B enzyme; Rifampicin
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.129675

The emergence of antibiotic-resistant and phage-resistant strains of Mycobacterium tuberculosis (M. tuberculosis) necessitates improving new therapeutic plans. The objective of the current work was to ensure the effectiveness of rifampicin and the mycobacteriophage LysB D29 (LysB)enzyme in the treatment of multi-drug resistant tuberculosis (MDR-TB) infection, where new and safe metal–organic framework (MOF) nanoparticles were used in combination. UiO-66 nanoparticles were synthesized under mild conditions in which the antimycobacterial agent (rifampicin) was loaded (Rif@UiO-66) and LysB D29 enzyme immobilized onto Rif@UiO-66, which were further characterized. Subsequently, the antibacterial activity of different ratios of Rif@UiO-66 and LysB/Rif@uio-66 against the nonpathogenic tuberculosis model Mycobacterium smegmatis (M. smegmatis) was evaluated by minimum inhibitory concentration (MIC) tests. Impressively, the MIC of LysB/Rif@uio-66 was 16-fold lower than that of pure rifampicin. In vitro and in vivo toxicity studies proved that LysB/Rif@UiO-66 is a highly biocompatible therapy for pulmonary infection. A biodistribution assay showed that LysB/Rif@UiO-66 showed a 5.31-fold higher drug concentration in the lungs than free rifampicin. A synergistic interaction between UiO-66, rifampicin and the mycobacteriophage lysB D29 enzyme was shown in the computational method (docking). Therefore, all results indicated that the LysB/Rif@UiO-66 nanocomposite exhibited promising innovative enzyme-antibiotic therapy for tuberculosis treatment. •We propose a potential synergistic enzyme-antibiotic therapy for enhanced anti-tubercular nanotherapeutics•The nanotherapeutic system overcomes the limitations associated with conventional treatments•Immobilization of Mycobacteriophage D29 LysinB enzyme onto Rif@UiO-66•Nano composite enables targeted and sustained release of therapeutic agents•Immobilized Mycobacteriophage D29 Lysin B enzyme onto Rif@UiO-66 nanocomposite.•The potential of the prepared nanotherapeutic system lies in its ability to overcome limitations associated with conventional treatments and provide a more effective approach against drug-resistant tuberculosis strain.•Potential synergistic enzyme-antibiotic therapy for enhanced antitubercular nanotherapeutics.