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Abstract：
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that replicates inside human alveolar macrophages. This disease causes significant morbidity and mortality throughout the world. According to the World Health Organization 1.4 million people died of this disease in 2021. This indicates that despite the progress of modern medicine, improvements in diagnostics, and the development of drug susceptibility tests, TB remains a global threat to public health. In this sense, host-directed therapy may provide a new approach to the cure of TB, and the expression of miRNAs has been correlated with a change in the concentration of various inflammatory mediators whose concentrations are responsible for the pathophysiology of M. tuberculosis infection. Thus, the administration of miRNAs may help to modulate the immune response of organisms. However, direct administration of miRNAs, without adequate encapsulation, exposes nucleic acids to the activity of cytosolic nucleases, limiting their application. Dendrimers are a family of highly branched molecules with a well-defined architecture and a branched conformation which gives rise to cavities that facilitate physical immobilization, and functional groups that allow chemical interaction with molecules of interest. Additionally, dendrimers can be easily functionalized to target different cells, macrophages among them. In this sense, various studies have proposed the use of different cell receptors as target molecules to aim dendrimers at macrophages and thus release drugs or nucleic acids in the cell of interest. Based on the considerations, the primary objective of this review is to comprehensively explore the potential of functionalized dendrimers as delivery vectors for miRNAs and other therapeutic agents into macrophages. This work aims to provide insights into the use of functionalized dendrimers as an innovative approach for TB treatment, focusing on their ability to target and deliver therapeutic cargo to macrophages.
摘要：
结核病（TB）是由结核分枝杆菌在人肺泡巨噬细胞内复制引起的传染病。这种疾病在全世界引起显著的发病率和死亡率。根据世界卫生组织的数据，2021年有140万人死于这种疾病。这表明，尽管现代医学取得了进步，诊断方面的改进，和药物敏感性试验的发展，结核病仍然是全球公共卫生的威胁。在这个意义上,以宿主为导向的治疗可能为结核病的治疗提供新的方法，miRNAs的表达与各种炎症介质的浓度变化相关，这些炎症介质的浓度与结核分枝杆菌感染的病理生理学有关。因此，miRNAs的施用可能有助于调节生物体的免疫应答。然而,直接施用miRNA，没有足够的封装，将核酸暴露于胞质核酸酶的活性，限制其应用。树枝状聚合物是一类高度支化的分子，具有明确的结构和分支构象，产生促进物理固定的空腔。和允许与感兴趣的分子发生化学相互作用的官能团。此外,树枝状聚合物可以很容易地功能化到不同的细胞，其中的巨噬细胞。在这个意义上,各种研究已经提出了使用不同的细胞受体作为靶分子来瞄准巨噬细胞的树状聚合物，从而在感兴趣的细胞中释放药物或核酸。基于考虑,本综述的主要目的是全面探索功能化树枝状聚合物作为miRNAs和其他治疗剂进入巨噬细胞的递送载体的潜力。这项工作旨在提供有关使用功能化树枝状聚合物作为结核病治疗创新方法的见解。专注于它们靶向和向巨噬细胞递送治疗性货物的能力。
