Laboratory of Experimental Therapy in Oncology, Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genoa, Italy.
Int J Mol Sci. 2018 Jul 4;19(7):1953. doi: 10.3390/ijms19071953.
Macrophages, cells belonging to the innate immune system, present a high plasticity grade, being able to change their phenotype in response to environmental stimuli. They play central roles during development, homeostatic tissue processes, tissue repair, and immunity. Furthermore, it is recognized that macrophages are involved in chronic inflammation and that they play central roles in inflammatory diseases and cancer. Due to their large involvement in the pathogenesis of several types of human diseases, macrophages are considered to be relevant therapeutic targets. Nanotechnology-based systems have attracted a lot of attention in this field, gaining a pivotal role as useful moieties to target macrophages in diseased tissues. Among the different approaches that can target macrophages, the most radical is represented by their depletion, commonly obtained by means of clodronate-containing liposomal formulations and/or depleting antibodies. These strategies have produced encouraging results in experimental mouse models. In this review, we focus on macrophage targeting, based on the results so far obtained in preclinical models of inflammatory diseases and cancer. Pros and cons of these therapeutic interventions will be highlighted.
巨噬细胞属于先天免疫系统的细胞,具有很高的可塑性,可以根据环境刺激改变其表型。它们在发育、组织稳态过程、组织修复和免疫中发挥核心作用。此外,人们已经认识到巨噬细胞参与慢性炎症,并且在炎症性疾病和癌症中发挥核心作用。由于它们在多种类型的人类疾病的发病机制中大量参与,因此巨噬细胞被认为是相关的治疗靶点。基于纳米技术的系统在该领域引起了广泛关注,作为靶向病变组织中巨噬细胞的有用部分,发挥了关键作用。在可以靶向巨噬细胞的不同方法中,最激进的方法是耗尽它们,通常通过含有氯膦酸盐的脂质体制剂和/或耗竭抗体来实现。这些策略在实验性小鼠模型中取得了令人鼓舞的结果。在这篇综述中,我们将基于目前在炎症性疾病和癌症的临床前模型中获得的结果,重点介绍巨噬细胞的靶向作用。我们将强调这些治疗干预措施的优缺点。