Farrell Kristen B, Karpeisky Alexander, Thamm Douglas H, Zinnen Shawn
MBC Pharma Inc., 12635 East Montview Blvd., Aurora, CO 80045-0100, United States of America.
Flint Animal Cancer Center, Colorado State University, 300 West Drake Road, Fort Collins, CO 80523-1620, United States of America.
Bone Rep. 2018 Jul 3;9:47-60. doi: 10.1016/j.bonr.2018.06.007. eCollection 2018 Dec.
Bones provide essential functions and are sites of unique biochemistry and specialized cells, but can also be sites of disease. The treatment of bone disorders and neoplasia has presented difficulties in the past, and improved delivery of drugs to bone remains an important goal for achieving effective treatments. Drug targeting strategies have improved drug localization to bone by taking advantage of the high mineral concentration unique to the bone hydroxyapatite matrix, as well as tissue-specific cell types. The bisphosphonate molecule class binds specifically to hydroxyapatite and inhibits osteoclast resorption of bone, providing direct treatment for degenerative bone disorders, and as emerging evidence suggests, cancer. These bone-binding molecules also provide the opportunity to deliver other drugs specifically to bone by bisphosphonate conjugation. Bisphosphonate bone-targeted therapies have been successful in treatment of osteoporosis, primary and metastatic neoplasms of the bone, and other bone disorders, as well as refining bone imaging. In this review, we focus upon the use of bisphosphonate conjugates with antineoplastic agents, and overview bisphosphonate based imaging agents, nanoparticles, and other drugs. We also discuss linker design potential and the current state of bisphosphonate conjugate research progress. Ongoing investigations continue to expand the possibilities for bone-targeted therapeutics and for extending their reach into clinical practice.
骨骼具有重要功能，是独特生物化学过程和特殊细胞的所在部位，但也可能成为疾病的病灶。过去，骨骼疾病和肿瘤的治疗面临诸多困难，提高药物在骨骼中的递送效率仍然是实现有效治疗的重要目标。药物靶向策略利用骨骼羟基磷灰石基质特有的高矿物质浓度以及组织特异性细胞类型，改善了药物在骨骼中的定位。双膦酸盐类分子特异性结合羟基磷灰石并抑制破骨细胞对骨骼的吸收，为退行性骨骼疾病以及新兴证据表明的癌症提供直接治疗。这些与骨骼结合的分子还提供了通过双膦酸盐偶联将其他药物特异性递送至骨骼的机会。双膦酸盐靶向疗法在治疗骨质疏松症、原发性和转移性骨肿瘤及其他骨骼疾病以及改进骨成像方面取得了成功。在本综述中，我们重点关注双膦酸盐与抗肿瘤药物的偶联物，并概述基于双膦酸盐的成像剂、纳米颗粒和其他药物。我们还讨论了连接子设计潜力以及双膦酸盐偶联物研究进展的现状。正在进行的研究不断拓展骨骼靶向治疗的可能性，并将其应用范围扩大到临床实践。
