Biologically-coupled bisphosphonate chaperones effectively deliver molecules to the site of soft tissue-bone healing.
Biologically-coupled bisphosphonate chaperones effectively deliver molecules to the site of soft tissue-bone healing.
复制标题
生物耦合的双膦酸盐分子伴侣可有效地将分子递送至软组织-骨愈合部位。
DOI：
10.1002/jor.25579
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Nishimura,Ichiro
中科院分区：
文献类型：
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作者：
KremenJr,ThomasJ;Shi,BrendanY;Wu,ShannonY;Sundberg,Oskar;Sriram,Varun;Kim,Won;Sheyn,Dmitriy;Lyons,KarenM;Wang,Weiguang;McKenna,CharlesE;Nishimura,Ichiro
肌腱损伤是常见的，并且通常通过手术治疗，然而，目前的肌腱修复愈合导致组织不良的纤维化组织。虽然已经报道某些生长因子可以改善修复的附着点的强度和组织，但由于缺乏适当的输送策略，它们的临床适用性受到严重限制。在这项研究中，我们评估了一种最近开发的荧光探针，骨吸附荧光哨兵-3，它由一个骨靶向双膦酸盐（BP）部分连接到荧光染料和淬灭剂分子，通过组织蛋白酶K敏感肽序列连接。使用小鼠跟腱-骨修复模型，局部或全身应用基于BP和/或Ctsk偶联的成像探针。荧光成像用于在体内定量所得信号。肌腱-骨修复后，接受局部或全身给予成像探针的动物在所有时间点均显示修复部位的荧光信号显著高于假手术组（p< 0.001），信号在术后7-10天达到峰值。我们的研究结果证明了使用新的基于BP的靶向和Ctsk激活的分子递送到肌腱-骨修复部位的可行性，并为进一步开发该平台作为将生物活性分子递送到肌肉骨骼损伤部位的有效策略奠定了基础。
Tendon injuries are common and often treated surgically, however, current tendon repair healing results in poorly organized fibrotic tissue. While certain growth factors have been reported to improve both the strength and organization of the repaired enthesis, their clinical applicability is severely limited due to a lack of appropriate delivery strategies. In this study, we evaluated a recently developed fluorescent probe, Osteoadsorptive Fluorogenic Sentinel‐3 that is composed of a bone‐targeting bisphosphonate (BP) moiety linked to fluorochrome and quencher molecules joined via a cathepsin K‐sensitive peptide sequence. Using a murine Achilles tendon‐to‐bone repair model, BP‐based and/or Ctsk‐coupled imaging probes were applied either locally or systemically. Fluorescence imaging was used to quantify the resultant signal in vivo. After tendon‐bone repair, animals that received either local or systemic administration of imaging probes demonstrated significantly higher fluorescence signal at the repair site compared to the sham surgery group at all time points (p< 0.001), with signal peaking at 7–10 days after surgery. Our findings demonstrate the feasibility of using a novel BP‐based targeting and Ctsk‐activated delivery of molecules to the site of tendon‐to‐bone repair and creates a foundation for further development of this platform as an effective strategy to deliver bioactive molecules to sites of musculoskeletal injury.