文献类型：期刊文献

英文题名：Precision-targeted nanodelivery systems for intra-articular treatment of knee osteoarthritis: recent breakthroughs and translational challenges

作者：Zhao, Yongli[1];Gao, Yaxiong[1];Zhao, Wenhua[2];Li, Fadong[3];Hou, WeiBing[4];Bu, Tiansheng[5]

第一作者：赵永利

通信作者：Bu, TS[1]

机构：[1]Gansu Univ Chinese Med, Affiliated Hosp, Lanzhou, Peoples R China;[2]Hefei Univ Technol, Sch Food & Biol Engn, Hefei, Anhui, Peoples R China;[3]Gansu Univ Chinese Med, Lanzhou, Gansu, Peoples R China;[4]Gansu Hlth Vocat Coll, Lanzhou, Gansu, Peoples R China;[5]First Peoples Hosp Baiyin City, Baiyin, Gansu, Peoples R China

第一机构：甘肃中医药大学第二附属医院

通信机构：[1]corresponding author), First Peoples Hosp Baiyin City, Baiyin, Gansu, Peoples R China.

年份：2026

卷号：14

外文期刊名：FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY

收录：;EI(收录号：20262420878853);Scopus(收录号：2-s2.0-105041206721);WOS:【SCI-EXPANDED(收录号:WOS:001780313900001)】；

基金：The author(s) declared that financial support was received for this work and/or its publication. This work was supported by Gansu Province University Industry Support Plan Project (2023CYZC-57),University (College)-Enterprise "Open Call for Leadership" Project (HXLH-JBGSO1),Gansu Province Key Project of Traditional Chinese Medicine Scientific Research (GZKZ-2024-9),Gansu Province Key Research Topic of Traditional Chinese Medicine Scientific Research (GZKZ-2020-6),Gansu Province Major Science and Technology Special Program (22ZD6FA021-4),Lanzhou Science and Technology Plan Project (2024-2-26),Lanzhou Science and Technology Plan Project (No. 2025-5-134), Gansu Province Health Industry Scientific Research Program Project (GSWSKY2022-61), Gansu Province Youth Science and Technology Fund Program (2020-0406-JCC-0452),At the same time, we also appreciate the support of the 2025 Clinical Key Specialty Capability Enhancement Project (Geriatric Orthopedics),the National Traditional Chinese Medicine Advantage Specialty (Orthopedics) and 2026 Gansu Province Clinical Key Specialty Capacity Enhancement Project (Acupuncture).

语种：英文

外文关键词：cartilage penetration; intra-articular nanodelivery; knee osteoarthritis; mesenchymal stem cell-derived exosomes; precision-targeted nanoparticles; stimuli-responsive release; theranostic nanoplatforms

摘要：Knee osteoarthritis (KOA) is a progressive whole-joint disorder characterized by cartilage degeneration, synovial inflammation, subchondral bone remodeling, and pathological alterations of the intra-articular (IA) microenvironment. Conventional IA therapies-including corticosteroids, hyaluronic acid, and emerging biologics-provide only transient relief due to rapid synovial clearance, poor cartilage penetration, and limited targeting specificity. Recent advances in nanotechnology have enabled the development of precision-targeted IA nanodelivery systems capable of overcoming anatomical, biomechanical, and biochemical barriers inherent to the osteoarthritic joint. This review summarizes recent breakthroughs in the rational engineering of nanocarriers, including optimization of physicochemical parameters, cartilage- and cell-specific targeting ligands, microenvironment-responsive release mechanisms, lubricating and mechanically adaptive nanomaterials, and integrated theranostic platforms. Progress in preclinical rodent and large-animal models is evaluated, alongside emerging translational evidence and early clinical experience. Remaining challenges-including long-term biocompatibility, pharmacokinetic heterogeneity across OA phenotypes, scalable manufacturing, and regulatory classification-are critically discussed. We highlight future directions centered on personalized nanotherapy, artificial intelligence-assisted carrier design, human-relevant joint organoids, and phenotype-stratified clinical trials. Collectively, precision-targeted IA nanodelivery represents a promising frontier toward clinically viable disease-modifying osteoarthritis drugs (DMOADs) and may ultimately shift KOA treatment from symptomatic management to true disease modification.