The systemic administration of drugs to treat bone diseases is often associated with poor uptake of the drug in the targeted tissue, potential systemic toxicity and suboptimal efficacy. In order to overcome these limitations, many micro- and nano-sized drug carriers have been developed for the treatment of bone pathologies that exhibit specific affinity for bone. Drug carriers can be functionalized with bone mineral seekers (BMS), creating a targeted drug delivery system (DDS) which is able to bind to bone and release therapeutics directly at the site of interest. This class of advanced DDS is of tremendous interest due to their strong affinity to bone, with great expectation to treat life-threatening bone disorders such as osteomyelitis, osteosarcoma or even osteoporosis. In this review, we first explain the mechanisms behind the affinity of several well-known BMS to bone, and then we present several effective approaches allowing the incorporation BMS into advanced DDS. Finally, we report the therapeutic applications of BMS based DDS under development or already established. Understanding the mechanisms behind the biological activity of recently developed BMS and their integration into advanced therapeutic delivery systems are essential prerequisites for further development of bone-targeting therapies with optimal efficacy.

药物用于全身性治疗骨疾病的系统性给药通常与目标组织中药物的吸收不良，潜在的全身毒性和次佳疗效有关。为了克服这些限制，已经开发出许多微米和纳米尺寸的药物载体用于治疗对骨表现出特异性亲和力的骨病理学。可以使用骨矿物质搜寻器（BMS）对药物载体进行功能化，从而创建靶向药物递送系统（DDS），该系统能够与骨骼结合并直接在目标部位释放治疗剂。这类高级DDS由于其对骨骼的强亲和力而备受关注，并有望治疗威胁生命的骨骼疾病，如骨髓炎，骨肉瘤甚至骨质疏松症。在这篇评论中，我们首先解释几种知名BMS与骨骼之间亲和力的机制，然后我们提出几种有效的方法，使BMS并入高级DDS。最后，我们报告了正在开发或已经建立的基于BMS的DDS的治疗应用。了解最新开发的BMS的生物学活性背后的机制以及将其整合到先进的治疗传递系统中是进一步开发具有最佳疗效的骨靶向疗法的基本前提。