Zhu Zhenglin, Luo Yujia, Xiao Pengcheng, Xie Yi, Zhang Jun, Huang Ke, Wu Xiangdong, Lu Ke, Zhang Yuting, Tan Jianye, Chen Hong, Huang Wei, Lei Yiting, Liao Junyi
Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine, Chongqing, 400016, China.
J Nanobiotechnology. 2025 Aug 4;23(1):551. doi: 10.1186/s12951-025-03598-2.
Osteoarthritis (OA) represents a major global health challenge, characterized by progressive cartilage degeneration and subchondral bone remodeling, which culminate in debilitating pain and functional impairment. While recent studies have underscored the pivotal role of activated osteoclasts in the pathogenesis of OA and its associated pain, the therapeutic potential of intra-articular drug delivery has been hindered by challenges such as rapid synovial clearance and the poor permeability of cartilage, limiting the effective inhibition of subchondral osteoclast activity.
Sixth generation polyamidoamine (PAMAM) dendrimers were used to delivery pamidronate disodium (PD) penetrating cartilage (PD@PM). PD@PM was loaded in aldehyde modified hyaluronic acid methacrylate (AHAMA) (PD@PM@MG), to facilitating the joint injection and conglutinating on the cartilage. Therapeutic effects of PD@PM@MG were validated by in vitro and in vivo OA models.
PD@PM@MGs microspheres are uniformly distributed across the cartilage surface and sustained releasing of PD-loaded PAMAM. The positively charged PD-loaded PAMAM (< 10 nm) efficiently permeates the cartilage matrix, neutralizes damage-associated molecular patterns, and effectively inhibits subchondral osteoclasts activities. Mice OA model tests demonstrated that intra-articular injection of PD@PM@MGs markedly alleviated arthritic pain, mitigated cartilage degeneration, and attenuated subchondral bone remodeling.
The intra-articular injection of PD@PM@MGs significantly alleviates OA symptoms and progression, offering a novel direction for clinical OA intervention.
[Image: see text]
The online version contains supplementary material available at 10.1186/s12951-025-03598-2.
骨关节炎（OA）是一项重大的全球健康挑战，其特征为软骨进行性退变和软骨下骨重塑，最终导致使人衰弱的疼痛和功能障碍。虽然最近的研究强调了活化破骨细胞在OA发病机制及其相关疼痛中的关键作用，但关节内给药的治疗潜力受到诸如滑膜快速清除和软骨通透性差等挑战的阻碍，限制了对软骨下破骨细胞活性的有效抑制。
使用第六代聚酰胺-胺（PAMAM）树枝状大分子递送穿透软骨的帕米膦酸二钠（PD）（PD@PM）。将PD@PM负载于醛修饰的甲基丙烯酸透明质酸（AHAMA）中（PD@PM@MG），以促进关节内注射并黏附于软骨上。通过体外和体内OA模型验证了PD@PM@MG的治疗效果。
PD@PM@MG微球均匀分布在软骨表面，并持续释放负载PD的PAMAM。带正电荷的负载PD的PAMAM（<10 nm）能有效穿透软骨基质，中和损伤相关分子模式，并有效抑制软骨下破骨细胞的活性。小鼠OA模型试验表明，关节内注射PD@PM@MG可显著减轻关节疼痛，减轻软骨退变，并减轻软骨下骨重塑。
关节内注射PD@PM@MG可显著减轻OA症状和病情进展，为临床OA干预提供了新的方向。
[图像：见正文]
在线版本包含可在10.1186/s12951-025-03598-2获取的补充材料。
