Sanhueza Claudia, Vergara Daniela, Chávez-Aravena Catalina, Gálvez-Jiron Felipe, Chavez-Angel Emigdio, Castro-Alvarez Alejandro
Centro de Excelencia en Medicina Traslacional (CEMT), Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile.
Departamento de Ciencias Preclínicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4811230, Chile.
Pharmaceuticals (Basel). 2023 Oct 9;16(10):1428. doi: 10.3390/ph16101428.
Tuberculosis (TB) is an infectious disease caused by 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 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.
结核病（TB）是一种由在人类肺泡巨噬细胞内复制的[病原体名称缺失]引起的传染病。这种疾病在全球范围内导致了严重的发病率和死亡率。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，诊断方法有所改进，药敏试验也得到了发展，但结核病仍然是对全球公共卫生的一大威胁。从这个意义上说，宿主导向疗法可能为结核病的治疗提供一种新方法，而且微小RNA（miRNA）的表达与多种炎症介质浓度的变化相关，这些炎症介质的浓度与[感染名称缺失]的病理生理学有关。因此，施用miRNA可能有助于调节生物体的免疫反应。然而，未经适当封装直接施用miRNA会使核酸暴露于胞质核酸酶的活性之下，从而限制了它们的应用。树枝状大分子是一类具有明确结构和分支构象的高度分支分子，其分支构象会形成便于物理固定的空腔以及允许与感兴趣分子进行化学相互作用的官能团。此外，树枝状大分子可以很容易地进行功能化修饰以靶向不同细胞，其中包括巨噬细胞。从这个意义上说，各种研究都提出使用不同的细胞受体作为靶分子，以使树枝状大分子靶向巨噬细胞，从而在目标细胞中释放药物或核酸。基于这些考虑，本综述的主要目的是全面探讨功能化树枝状大分子作为miRNA和其他治疗剂递送至巨噬细胞的载体的潜力。这项工作旨在深入了解使用功能化树枝状大分子作为结核病治疗的创新方法，重点关注其靶向并将治疗性货物递送至巨噬细胞的能力。
