Self-Reinforced MOF-Based Nanogel Alleviates Osteoarthritis by Long-Acting Drug Release

Bibliographische Detailangaben
Veröffentlicht in:	Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 39 vom: 01. Sept., Seite e2401094
1. Verfasser:	Sun, Yun (VerfasserIn)
Weitere Verfasser:	Ding, Sheng-Long, Zhao, Xiyuan, Sun, Dadi, Yang, Yuhan, Chen, Min, Zhu, Chunlin, Jiang, Bingyin, Gu, Qi, Liu, Huiyu, Zhang, Mingzhu
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2024
Zugriff auf das übergeordnete Werk:	Advanced materials (Deerfield Beach, Fla.)
Schlagworte:	Journal Article cartilage regeneration kartogenin osteoarthritis zeolitic imidazolate frameworks Hyaluronic Acid 9004-61-9 Q93BBN11CP Nanogels Metal-Organic Frameworks mehr... Anilides Phthalic Acids Delayed-Action Preparations Polyethylene Glycols 3WJQ0SDW1A Drug Carriers Imidazoles polyethylene glycol polyethyleneimine nanogel Polyethyleneimine 9002-98-6

Beschreibung
Zusammenfassung:	© 2024 Wiley‐VCH GmbH. Intra-articular injection of drugs is an effective strategy for osteoarthritis (OA) treatment. However, the complex microenvironment and limited joint space result in rapid clearance of drugs. Herein, a nanogel-based strategy is proposed for prolonged drug delivery and microenvironment remodeling. Nanogel is constructed through the functionalization of hyaluronic acid (HA) by amide reaction on the surface of Kartogenin (KGN)-loaded zeolitic imidazolate framework-8 (denoted as KZIFHA). Leveraging the inherent hydrophilicity of HA, KZIF@HA spontaneously forms nanogels, ensuring extended drug release in the OA microenvironment. KZIF@HA exhibits sustained drug release over one month, with low leakage risk from the joint cavity compared to KZIF, enhanced cartilage penetration, and reparative effects on chondrocytes. Notably, KGN released from KZIF@HA serves to promote extracellular matrix (ECM) secretion for hyaline cartilage regeneration. Zn2+ release reverses OA progression by promoting M2 macrophage polarization to establish an anti-inflammatory microenvironment. Ultimately, KZIF@HA facilitates cartilage regeneration and OA alleviation within three months. Transcriptome sequencing validates that KZIF@HA stimulates the polarization of M2 macrophages and secretes IL-10 to inhibit the JNK and ERK pathways, promoting chondrocytes recovery and enhancing ECM remodeling. This pioneering nanogel system offers new therapeutic opportunities for sustained drug release, presenting a significant stride in OA treatment strategies
Beschreibung:	Date Completed 27.09.2024 Date Revised 27.09.2024 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-4095
DOI:	10.1002/adma.202401094