Dataset Information

DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy.

ABSTRACT: Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL-1β mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nanorods to fabricate the spherical nucleic acids (SNAs), to promote the stability and cell internalization efficiency. Furthermore, the complementary oligonucleotides are grafted onto hyaluronic acid (HA) to obtained DNA-grafted HA (^DNAHA) for SNAs delivery by base pairing, resulting in significantly improved injectability and bio-stability of the system. After loading SNAs, the constructed ^DNAHA-SNAs system (HA-SNAs) performs a reversible NIR-triggered on-demand release of SNAs by photo-thermal induced DNA dehybridization and followed by post-NIR in situ hybridization. The in vitro and in vivo experiments showed that this system down-regulated catabolic proteases and up-regulated anabolic components in cartilage over extended periods of time, to safeguard the chondrocytes against degenerative changes and impede the continual advancement of OA.

SUBMITTER: Chen Z

PROVIDER: S-EPMC8097319 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy.

Chen Zhijie Z Zhang Feng F Zhang Hongbo H Cheng Liang L Chen Kaizhe K Shen Jieliang J Qi Jin J Deng Lianfu L He Chuan C Santos Hélder A HA Cui Wenguo W

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20210301 9

Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL-1<i>β</i> mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nan ...[more]

PMID: 33977074

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Project description:Objective Osteoarthritis (OA) is a painful degenerative disease of the whole joint structure, including articular cartilage, synovial fluid, and subchondral bone. Hyaluronic acid (HA), an anionic non-sulfated glycosaminoglycan, is commonly used for intra-articular (IA) treatment in OA, while bisphosphonates (BPs) are anti-resorptive drugs that act on the bone. Here, a novel conjugate with a covalent and hydrolysable linker between HA and alendronate (ALD) was designed as an attractive therapeutic strategy for IA drug delivery. Design The HA-ALD derivative was synthesized and tested in comparison with a simple mixture of HA and ALD for in vitro ALD release, rheological properties, cytotoxicity towards osteoblasts and chondrocytes and in an in vitro efficacy assay of OA inflammatory model on bovine cartilage explants. Results The structure of HA-ALD was elucidated exhibiting no depolymerization and efficient drug incorporation. The controlled ALD release in vitro was slower compared to the simple mixture of HA and ALD; moreover, the derivative showed calcium-tuned rheological properties. The absence of cytotoxicity towards osteoblasts and chondrocytes was shown for up to 7 days, and the viability of chondrocytes was confirmed by fluorescence microscopy. Finally, a reduction in collagen release and MMP-13 expression was measured in the OA inflammatory model. Conclusion This new HA-ALD derivative opens the door to a new approach for OA treatment, as it combines viscosupplementation and biological effects of HA with the pharmacological activity of BPs. Prolonged ALD release increased rheological properties and beneficial effect against cartilage degradation make it a promising IA therapy for OA. Graphical abstract Image 1 Highlights • Development of an IA treatment to target OA pathogenesis rather than symptoms.• A novel hyaluronan-alendronate conjugate was synthesized with a reversible linker.• The drug delivery system confirmed slow alendronate release.• The efficacy was demonstrated in an osteoarthritis inflammatory model.• New intra-articular treatment: viscosupplementation and pharmacological activity.

Dataset Information

DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy.

Publications

DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy.

Similar Datasets

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