Effects of cartilage-targeting moieties on nanoparticle biodistribution in healthy and osteoarthritic joints
Effects of cartilage-targeting moieties on nanoparticle biodistribution in healthy and osteoarthritic joints
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DOI：
10.1016/j.actbio.2019.10.003
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发表时间：
2020-01-01
影响因子：
9.7
通讯作者：
Sharma, Blanka
中科院分区：
文献类型：
--
作者：
Brown, Shannon B.;Wang, Lei;Sharma, Blanka
随着骨关节炎（OA）候选药物越来越具有部位特异性，了解关节内生物分布势在必行。卡莫司已被确定为治疗干预的机会，但对药物递送造成许多障碍。为了促进药物输送到软骨，纳米级车辆已被设计成具有不同的功能，目标组织的基质。然而，目前尚不清楚这些靶向策略是否受到OA和软骨中发生的相关结构变化的影响。这项工作的目标是研究不同软骨靶向纳米材料在软骨定位和保留方面的有效性，并确定这些结果在OA中如何变化。为了解决这些问题，开发了纳米颗粒（NP）系统，并且将制剂调整为具有三种不同的软骨靶向策略：（1）用于静电吸引软骨的被动靶向阳离子NP，（2）具有II型胶原蛋白结合肽的主动靶向NP，以及（3）非靶向的带中性电荷的NP。用牛软骨外植体进行的离体分析表明，靶向策略显著改善了NP与健康软骨和OA样软骨的关联。在大鼠中胶原酶诱导的OA的体内研究显示，疾病状态影响所有三种NP制剂的关节生物分布。重要的是，每个NP系统的软骨积聚程度受疾病的影响不同;与主动NP相比，OA中的软骨积聚相对于健康膝关节增加，而被动NP则没有。总之，这项工作表明，纳米颗粒可以战略性地设计为特定于网站的OA药物输送，但纳米颗粒的生物分布的疾病条件，他们delivered.Statement of SignificanceAs新兴的药物骨关节炎正变得越来越具体的网站，有针对性的关节内药物输送的需要已经演变。为了改善药物向软骨的递送，已经开发了纳米材料的靶向策略，但是这些靶向系统在关节内不同部位积累的方式仍然知之甚少。此外，目前还不清楚纳米材料-组织相互作用在骨关节炎条件下如何变化，因为疾病发作后组织结构和组成发生变化。通过了解纳米材料如何在健康和疾病关节中分布，我们可以推进靶向药物递送策略，并改善新兴药物的治疗效果。(C)2019 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Understanding intra-articular biodistribution is imperative as candidate osteoarthritis (OA) drugs become increasingly site-specific. Cartilage has been identified as opportunistic for therapeutic intervention, but poses numerous barriers to drug delivery. To facilitate drug delivery to cartilage, nanoscale vehicles have been designed with different features that target the tissue's matrix. However, it is unclear if these targeting strategies are influenced by OA and the associated structural changes that occur in cartilage. The goal of this work was to study the effectiveness of different cartilage-targeting nanomaterials with respect to cartilage localization and retention, and to determine how these outcomes change in OA. To address these questions, a nanoparticle (NP) system was developed, and the formulation was tuned to possess three distinct cartilage-targeting strategies: (1) passive targeting cationic NPs for electrostatic attraction to cartilage, (2) active targeting NPs with binding peptides for collagen type II, and (3) untargeted neutrally-charged NPs. Ex vivo analyses with bovine cartilage explants demonstrated that targeting strategies significantly improved NP associations with both healthy and OA-like cartilage. In vivo studies with collagenase-induced OA in rats revealed that disease state influenced joint biodistribution for all three NP formulations. Importantly, the extent of cartilage accumulation for each NP system was affected by disease differently; with active NPs, but not passive NPs, cartilage accumulation was increased in OA relative to healthy knees. Together, this work suggests that NPs can be strategically designed for site-specific OA drug delivery, but the biodistribution of the NPs are influenced by the disease conditions into which they are delivered.Statement of SignificanceAs emerging drugs for osteoarthritis are becoming increasingly site-specific, the need for targeted intraarticular drug delivery has evolved. To improve drug delivery to cartilage, targeting strategies for nano materials have been developed, but the manner in which these targeted systems accumulate at different sites within the joint remains poorly understood. Moreover, it is unclear how nanomaterial-tissue interactions change in osteoarthritic conditions, as tissue structure and composition change after disease onset. By understanding how nanomaterials distribute within healthy and disease joints, we can advance targeted drug delivery strategies and improve therapeutic outcomes for emerging drugs. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.