Scholarlink

<p>Osteoarthritis (OA) affects a large population worldwide, causing chronic pain, functional decline, and increased personal and societal medical costs. A major challenge in developing disease-modifying OA drugs (DMOADs) is the inefficient delivery to diseased chondrocytes. Here we synthesize a viral glycoprotein-mimicking peptide (CMP) containing a type II collagen-adhesive motif and a matrix metalloproteinase-13-activated cell-penetrating peptide sequence. The CMP peptide was conjugated to small-sized micelles loaded with the model drug IOX4, enabling the micelles to adhere to cartilage and chondrocyte surfaces through collagen binding and achieve proteinase-induced selective uptake by diseased chondrocytes. In an OA mouse model, our micelles demonstrated prolonged joint retention and exhibited a higher uptake by diseased chondrocytes compared with unmodified micelles and normal chondrocytes, respectively. In both OA mice and a clinically relevant OA sheep model, our system maintained metabolic homeostasis in cartilage, attenuating OA pathological changes and improving symptoms without causing additional toxicity. These findings suggest that our nanoformulation is a promising DMOAD candidate and provides an efficient delivery strategy for other potential DMOADs targeting intracellular sites of diseased chondrocytes.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Viral glycoprotein-mimicking peptide-functionalized micelles promote drug delivery to diseased chondrocytes for osteoarthritis alleviation

  • 期刊论文

  • 发表日期：

    2025年12月29日

查看全文
  • Xiao Chen,
  • Dongyang Zhou,
  • Jian Wang,
  • Han Liu,
  • Hao Zhang,
  • Zhen Geng,
  • Guangchao Wang,
  • Hao Shen,
  • Yuanwei Zhang,
  • Zuhao Li,
  • Dongliang Wang,
  • Xiaoxiang Ren,
  • Xiuhui Wang,
  • Ke Xu,
  • Chongru He,
  • Long Bai,
  • Yan Wei,
  • Xiaoyuan Chen,
  • Jiacan Su

摘要

Osteoarthritis (OA) affects a large population worldwide, causing chronic pain, functional decline, and increased personal and societal medical costs. A major challenge in developing disease-modifying OA drugs (DMOADs) is the inefficient delivery to diseased chondrocytes. Here we synthesize a viral glycoprotein-mimicking peptide (CMP) containing a type II collagen-adhesive motif and a matrix metalloproteinase-13-activated cell-penetrating peptide sequence. The CMP peptide was conjugated to small-sized micelles loaded with the model drug IOX4, enabling the micelles to adhere to cartilage and chondrocyte surfaces through collagen binding and achieve proteinase-induced selective uptake by diseased chondrocytes. In an OA mouse model, our micelles demonstrated prolonged joint retention and exhibited a higher uptake by diseased chondrocytes compared with unmodified micelles and normal chondrocytes, respectively. In both OA mice and a clinically relevant OA sheep model, our system maintained metabolic homeostasis in cartilage, attenuating OA pathological changes and improving symptoms without causing additional toxicity. These findings suggest that our nanoformulation is a promising DMOAD candidate and provides an efficient delivery strategy for other potential DMOADs targeting intracellular sites of diseased chondrocytes.