pH-responsive and hyaluronic acid-functionalized metal–organic frameworks for therapy of osteoarthritis

Abstract

Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal − organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1β induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA.

Metal organic framework-coated gold nanorod as an on-demand drug delivery platform for chemo-photothermal cancer therapy

“…Recently, metal–organic frameworks (MOFs), which composed of metal nodes and organic linkers, have emerged as promising materials for biomedical applications, such as drug delivery [ 26 , 27 ], catalysis [ 28 ], molecular imaging [ 29 ], and biosensing [ 30 ], due to their exceptional large surface area and tunable inner cavity. Among them, zeolitic imidazolate framework-8 (ZIF-8) with low-toxic Zn 2+ and 2-methylimidazole (2-MIN) as the basic units, was recognized as a biocompatible and acid-responsive drug carrier [ 31 ].…”

Implantable Polyacrylonitrile-Spermidine Electrospun Nanofibers with Sustainable ROS Scavening Capacity for Osteoarthritis (OA) Therapy

“…Previous studies have shown that ROS lead to chondrocyte apoptosis and cartilage degeneration which accelerate OA progression [33][34][35]. SPD could act as free radical scavengers, but it would be rapidly cleared from the joint cavity [13,36].…”

Metal-Organic Frameworks and Their Composites Towards Biomedical Applications

“…Apart from tumor regions, HA coating could target inflammation sites and also improve the water stability of MOFs. Significantly, HA on the surface of MOFs also alleviates inflammation by reducing the expression of cytokines (Xiong et al, 2020).…”

“…As for microenvironment and pathogenesis, Xiong et al engineered an intelligent pH-responsive drug delivery system modified by hydrophilic agent HA, which could improve the hydrophilicity of MOFs and inflammation of OA simultaneously. In the weak acidic environment of osteoarthritis (OA), MIL-100(Fe) was disrupted, and protocatechuic acid (PCA) was released for alleviating inflammation by reducing the inflammatory mediators (Xiong et al, 2020). Similarly, as mentioned above, an oxidation-responsive MOF, Ce-MOF@ PSS, was designed based on the microenvironment of inflammatory bowel disease (IBD) and antioxidant ability of Ce 3+ /Ce 4+ .…”