Intracellular Delivery of Itaconate by Metal–Organic Framework-Anchored Hydrogel Microspheres for Osteoarthritis Therapy
Han Yu,
Peng Ren,
Xuekang Pan,
Xinyu Zhang,
Jun Ma,
Jiayi Chen,
Jian Sheng,
Huanhuan Luo,
Huigen Lu,
Gang Chen
Affiliations
Han Yu
Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou 310000, China
Peng Ren
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, China
Xuekang Pan
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, China
Xinyu Zhang
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, China
Jun Ma
Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical University, Hangzhou 310000, China
Jiayi Chen
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, China
Jian Sheng
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, China
Huanhuan Luo
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, China
Huigen Lu
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, China
Gang Chen
Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, Department of Orthopaedics, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, China
Treatment of osteoarthritis (OA) remains a significant clinical challenge. Itaconate (IA), an emerging regulator of intracellular inflammation and oxidative stress, may potentially be harnessed to treat OA. However, the short joint residence time, inefficient drug delivery, and cell-impermeable property of IA can seriously hamper the clinical translation. Herein, IA-encapsulated zeolitic imidazolate framework-8 (IA-ZIF-8) nanoparticles were self-assembled by zinc ions, 2-methylimidazole, and IA to render them pH-responsive. Subsequently, IA-ZIF-8 nanoparticles were firmly immobilized in hydrogel microspheres via one-step microfluidic technology. It was demonstrated in vitro experiments that IA-ZIF-8-loaded hydrogel microspheres (IA-ZIF-8@HMs) exhibited good anti-inflammatory and anti-oxidative stress effects by releasing pH-responsive nanoparticles into chondrocytes. Importantly, compared with IA-ZIF-8, IA-ZIF-8@HMs showed better performance in the treatment of OA due to their superior performance in sustained release. Thus, such hydrogel microspheres not only hold enormous potential for OA therapy, but also provide a novel avenue for cell-impermeable drugs by constructing appropriate drug delivery systems.
