骨发育具有复杂的调节机制,包括信号转导和转录因子相关通路,糖生物学过程,细胞相互作用,运输机制,and,重要的是,羟基磷灰石产生的化学形成。骨骼发育过程中的任何异常调节都会导致骨骼系统相关问题。在某种程度上,软骨和骨的无血管性使药物输送比软组织更具挑战性。最近的研究已经实施了许多新颖的骨靶向方法来克服缺点。然而,这些策略都不能完全纠正骨骼功能障碍,特别是与生长板相关的。虽然直接重组酶(例如,Vimizim代表Morquio,高彻的谷物酶,猎人的行动,用于Sly疾病的Mepsevii)或激素输注(用于骨质疏松症和骨关节炎的雌激素),传统的基因传递(例如,直接输注病毒或非病毒载体,衣壳上没有修饰,信封,或纳米粒子),和细胞治疗策略(健康骨髓或造血干细胞移植)部分改善骨病变,必须解决新的递送方法关于靶特异性,免疫原性较低,和循环持续时间。除了改善骨输送,还利用了涉及受体调节途径的骨发育机制的潜在调节。使用有机和无机化合物的靶向药物递送在大多数临床前环境和未来临床转化中是有希望的方法。这篇综述全面总结了当前基于骨结构和重塑概念的骨靶向策略,同时强调了未来骨靶向系统的潜在方法。
Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. However, none of these strategies fully corrects skeletal dysfunction, particularly in growth plate-related ones. Although direct recombinant enzymes (e.g., Vimizim for Morquio, Cerezyme for Gaucher, Elaprase for Hunter, Mepsevii for Sly diseases) or hormone infusions (estrogen for osteoporosis and osteoarthritis), traditional gene delivery (e.g., direct infusion of viral or non-viral vectors with no modifications on capsid, envelope, or nanoparticles), and cell therapy strategies (healthy bone marrow or hematopoietic stem cell transplantation) partially improve bone lesions, novel delivery methods must be addressed regarding target specificity, less immunogenicity, and duration in circulation. In addition to improvements in bone delivery, potential regulation of bone development mechanisms involving receptor-regulated pathways has also been utilized. Targeted drug delivery using organic and inorganic compounds is a promising approach in mostly preclinical settings and future clinical translation. This review comprehensively summarizes the current bone-targeting strategies based on bone structure and remodeling concepts while emphasizing potential approaches for future bone-targeting systems.