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Cartilage‐targeting ultrasmall lipid‐polymer hybrid nanoparticles for the prevention of cartilage degradation
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2020-09-01 , DOI: 10.1002/btm2.10187 Xiangzhao Ai 1 , Yaou Duan 1 , Qiangzhe Zhang 1 , Derrick Sun 1 , Ronnie H Fang 1 , Ru Liu-Bryan 2 , Weiwei Gao 1 , Liangfang Zhang 1
Bioengineering & Translational Medicine ( IF 6.1 ) Pub Date : 2020-09-01 , DOI: 10.1002/btm2.10187 Xiangzhao Ai 1 , Yaou Duan 1 , Qiangzhe Zhang 1 , Derrick Sun 1 , Ronnie H Fang 1 , Ru Liu-Bryan 2 , Weiwei Gao 1 , Liangfang Zhang 1
Affiliation
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Current drug delivery approaches for the treatment of cartilage disorders such as osteoarthritis (OA) remain inadequate to achieve sufficient drug penetration and retention in the dense cartilage matrix. Herein, we synthesize sub‐30 nm lipid‐polymer hybrid nanoparticles functionalized with collagen‐targeting peptides for targeted drug delivery to the cartilage. The nanoparticles consist of a polymeric core for drug encapsulation and a lipid shell modified with a collagen‐binding peptide. By combining these design features, the nanoparticles can penetrate deep and accumulate preferentially in the cartilage. Using MK‐8722, an activator of 5′‐adenosine monophosphate‐activated protein kinase (AMPK), as a model drug, the nanoparticles can encapsulate the drug molecules in high capacity and release them in a sustained and controllable manner. When injected into the knee joints of the mice with collagenase‐induced OA, the drug‐loaded nanoparticles can effectively reduce cartilage damage and alleviate the disease severity. Overall, the ultrasmall targeted nanoparticles represent a promising delivery platform to overcome barriers of dense tissues for the treatment of various indications, including cartilage disorders.
中文翻译：
软骨靶向超小脂质聚合物混合纳米粒子用于预防软骨退化
目前用于治疗骨关节炎（OA）等软骨疾病的药物递送方法仍然不足以实现足够的药物渗透和在致密软骨基质中的保留。在此，我们合成了用胶原蛋白靶向肽功能化的亚 30 nm 脂质聚合物杂化纳米颗粒，用于将靶向药物递送至软骨。纳米粒子由用于药物封装的聚合物核心和用胶原蛋白结合肽修饰的脂质壳组成。通过结合这些设计特征，纳米颗粒可以深入渗透并优先积聚在软骨中。以5'-单磷酸腺苷激活蛋白激酶（AMPK）激活剂MK-8722为模型药物，纳米颗粒可以高容量封装药物分子并持续可控地释放它们。当将载药纳米粒子注射到胶原酶诱导的 OA 小鼠的膝关节中时，可以有效减少软骨损伤并减轻疾病的严重程度。总体而言，超小型靶向纳米粒子代表了一个有前途的递送平台，可以克服致密组织的障碍，用于治疗包括软骨疾病在内的各种适应症。
更新日期：2020-09-01
中文翻译：
软骨靶向超小脂质聚合物混合纳米粒子用于预防软骨退化
目前用于治疗骨关节炎（OA）等软骨疾病的药物递送方法仍然不足以实现足够的药物渗透和在致密软骨基质中的保留。在此，我们合成了用胶原蛋白靶向肽功能化的亚 30 nm 脂质聚合物杂化纳米颗粒，用于将靶向药物递送至软骨。纳米粒子由用于药物封装的聚合物核心和用胶原蛋白结合肽修饰的脂质壳组成。通过结合这些设计特征，纳米颗粒可以深入渗透并优先积聚在软骨中。以5'-单磷酸腺苷激活蛋白激酶（AMPK）激活剂MK-8722为模型药物，纳米颗粒可以高容量封装药物分子并持续可控地释放它们。当将载药纳米粒子注射到胶原酶诱导的 OA 小鼠的膝关节中时，可以有效减少软骨损伤并减轻疾病的严重程度。总体而言，超小型靶向纳米粒子代表了一个有前途的递送平台，可以克服致密组织的障碍，用于治疗包括软骨疾病在内的各种适应症。
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