Shah Muddaser, Rehman Khadija, Khan Adnan, Farid Arshad, Marini Carlotta, Di Cerbo Alessandro, Shah Muhammad Raza
Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, Pakistan.
Department of Botany, Abdul Wali Khan University Mardan, Mardan 23200, Pakistan.
Polymers (Basel). 2022 Jul 1;14(13):2712. doi: 10.3390/polym14132712.
The emergence of bacterial resistance has increased the economic burden of infectious diseases dramatically during the previous few decades. Multidrug resistance (MDR) is difficult to cure in both Gram-negative and positive bacteria and is often incurable with traditional and broad-range antibiotics. Therefore, developing techniques to increase the antibacterial activity of therapeutic drugs is essential. Metal-organic frameworks (MOFs) are extremely versatile hybrid materials made of metal ions coupled via organic bridging ligands. They have been widely used as an excellent vehicle for drug delivery due to their low toxicity, biodegradability, and structural stability upon loading and functionalization. The present study focused on the synthesis of mannose (MNS)-coated MOFs with enhanced surface contact with cells. The MNS coating on the surface of MOFs enhances their adherence to bacteria by binding to lectins present on the bacterial cell, resulting in improved VCM cellular penetration and activity against resistant bacteria. Various techniques, including atomic force microscopy, DLS, TGA, FT-IR, and DSC, were employed to analyze MNS-coated MOFs. They were also evaluated for their efficacy against resistant . The results indicated that when VCM was loaded into MNS-coated MOFs, their bactericidal activity rose dramatically, resulting in the greater suppression of resistant . AFM investigation of strains demonstrated total morphological distortion after treatment with MNS-coated drug-loaded MOFs. The results of this work suggest that MNS-coated MOFs may be effective for reversing bacterial resistance to VCM and open new pathways for improving antibiotic therapy for diseases associated with MDR.
在过去几十年中，细菌耐药性的出现显著增加了传染病的经济负担。多重耐药性（MDR）在革兰氏阴性菌和阳性菌中都难以治愈，并且传统的广谱抗生素往往无法治愈。因此，开发提高治疗药物抗菌活性的技术至关重要。金属有机框架（MOF）是由金属离子通过有机桥联配体偶联而成的极具通用性的杂化材料。由于其低毒性、生物可降解性以及负载和功能化后的结构稳定性，它们已被广泛用作药物递送的优良载体。本研究专注于合成与细胞具有增强表面接触的甘露糖（MNS）包覆的MOF。MOF表面的MNS涂层通过与细菌细胞上存在的凝集素结合来增强其对细菌的粘附，从而提高万古霉素（VCM）的细胞穿透能力和对耐药菌的活性。采用了包括原子力显微镜、动态光散射、热重分析、傅里叶变换红外光谱和差示扫描量热法等各种技术来分析MNS包覆的MOF。还评估了它们对耐药菌的疗效。结果表明，当VCM负载到MNS包覆的MOF中时，其杀菌活性显著提高，从而对耐药菌有更大的抑制作用。对菌株的原子力显微镜研究表明，用MNS包覆的载药MOF处理后，其形态完全扭曲。这项工作的结果表明，MNS包覆的MOF可能对逆转细菌对VCM的耐药性有效，并为改善与MDR相关疾病的抗生素治疗开辟新途径。
