Stellpflug Austin, Joshi Amit, Wang Shue, Gu Linxia, Wu Rongxue, Wang Bo
Joint Department of Biomedical Engineering, Marquette University, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Department of Chemistry, Chemical and Biomedical Engineering, University of New Haven, West Haven, CT, 06516, USA.
Drug Deliv Transl Res. 2025 Sep 15. doi: 10.1007/s13346-025-01968-9.
Hydroxyapatite (HA)-binding peptides hold strong potential for bone-targeted therapies due to their high affinity for mineralized tissues. However, most existing studies have primarily focused on in vitro binding characterization, offering limited insight into their in vivo biodistribution and bone-binding performance. In this study, we evaluated the in vivo behavior of four HA-binding peptides, including D8, E8, YD8, and YE8, using fluorescence imaging to assess biodistribution in both healthy and pathological bone environments. In healthy animals, D8 showed the strongest bone-binding capacity, with prominent localization in the skull, femur, and tibia, while YD8 exhibited moderate binding. E8 and YE8 showed more limited localization, influenced by peptide dosage and binding kinetics. In pathological models, including tibial defects and osteogenesis imperfecta (OIM) mice, D8 and YD8 preferentially accumulated in compromised bone regions, highlighting their potential utility in targeting diseased bone microenvironments. Fluorescence imaging combined with spectral unmixing algorithms enabled effective visualization and quantification of peptide localization and distribution. These findings emphasize the value of in vivo studies for advancing the therapeutic and diagnostic applications of HA-binding peptides. The results provide a foundation for optimizing peptide design to improve specificity and efficacy in bone repair and regeneration.
由于羟基磷灰石（HA）结合肽对矿化组织具有高亲和力，因此在骨靶向治疗方面具有巨大潜力。然而，大多数现有研究主要集中在体外结合特性上，对其体内生物分布和骨结合性能的了解有限。在本研究中，我们使用荧光成像评估了四种HA结合肽（包括D8、E8、YD8和YE8）在健康和病理骨环境中的生物分布，从而评估了它们在体内的行为。在健康动物中，D8显示出最强的骨结合能力，在颅骨、股骨和胫骨中有明显定位，而YD8表现出中等结合能力。E8和YE8的定位更有限，受肽剂量和结合动力学影响。在包括胫骨缺损和成骨不全（OIM）小鼠在内的病理模型中，D8和YD8优先积聚在受损骨区域，突出了它们在靶向患病骨微环境方面的潜在用途。荧光成像与光谱解混算法相结合，能够有效地可视化和量化肽的定位和分布。这些发现强调了体内研究对于推进HA结合肽的治疗和诊断应用的价值。研究结果为优化肽设计以提高骨修复和再生的特异性和疗效奠定了基础。
