MMP13-targeted siRNA-loaded micelles for diagnosis and treatment of posttraumatic osteoarthritis

Zhou, Dongyang; Wei, Yan; Sheng, Shihao; Wang, Miaomiao; Lv, Jiajing; Zhao, Bowen; Chen, Xiao; Xu, Ke; Bai, Long; Wu, Yan; Song, Peiran; Cao, Liehu; Zhou, Fengjin; Zhang, Hao; Shi, Zhongmin; Su, Jiacan

doi:10.1016/j.bioactmat.2024.04.010

Cited by 6 publications

(1 citation statement)

References 49 publications

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“…These results further confirmed that the combination therapy obtained a better therapeutic effect than single Exo or DS treatment, indicating the superior therapeutic efficacy of MPM@Exo&DS in reversing the progression of OA. Because MMP13 is a key protein in the development of OA, we examined the expression of MMP13 after treatment by immunohistochemistry. , The results indicated that MPM@Exo&DS treated groups have the lowest MMP13 expression levels, suggesting that the released Exo and DS from MPM can restrain the activity of MMP13 and further alleviate the OA process (Figure c,f). In addition, the H&E staining of the main organs indicated that MPMs have good biocompatibility in vivo (Figure S9).…”

Section: Resultsmentioning

confidence: 98%

Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis

Yang,

Li,

Zhao

et al. 2024

ACS Nano

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Osteoarthritis (OA) is a prevalent degenerative disease that afflicts more than 250 million people worldwide, impairing their mobility and quality of life. However, conventional drug therapy is palliative. Exosomes (Exo), although with the potential to fundamentally repair cartilage, face challenges in their efficient enrichment and delivery. In this study, we developed magnetic polysaccharide hydrogel particles as microcarriers for synergistic therapy of OA. The microcarriers were composed of modified natural polysaccharides, hyaluronic acid (HAMA), and chondroitin sulfate (CSMA), and were generated from microfluidic electrospray in combination with a cryogelation process. Magnetic nanoparticles with spiny structures capable of capturing stem cell Exo were encapsulated within the microcarriers together with an anti-inflammatory drug diclofenac sodium (DS). The released DS and Exo from the microcarriers had a synergistic effect in alleviating the OA symptoms and promoting cartilage repair. The in vitro and in vivo results demonstrated the excellent performance of the microcarrier for OA treatment. We believe this work has potential for Exo therapy of OA and other related diseases.

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Section: Resultsmentioning

confidence: 98%

Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis

Yang,

Li,

Zhao

et al. 2024

ACS Nano

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Biomimetic Nano‐delivery of Small‐Molecule Piceatannol Modulates Tumor Stemness and Suppresses Colorectal Cancer Metastasis via Hippo/YAP1/SOX9 Signaling

Zhou,

Niu,

Huang

et al. 2024

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Suppressing tumor metastasis is a crucial strategy for improving survival rates in patients with colorectal cancer (CRC), with cancer stem cells (CSCs) being the primary drivers of metastasis. Current therapeutic approaches targeting CSCs are limited, and their molecular mechanisms remain unclear. To address this challenge, a biomimetic nanoparticle delivery system, CMD‐BHQ3‐PTL/DOX@RBCM is developed, to deliver the stem cell regulator, piceatannol (PTL). This system used carboxymethyl dextran (CMD) and Black Hole Quencher 3 (BHQ3) to encapsulate PTL and the cytotoxic drug doxorubicin (DOX) within a red blood cell membrane (RBCm), enhancing stability and biocompatibility while allowing gradual drug release under hypoxic conditions. The effects of PTL are investigated on CSCs using molecular biology experiments, plasmid construction, and high‐throughput sequencing and elucidated the molecular mechanisms underlying this biomimetic nanoparticle delivery system. The therapeutic efficacy of PTL is validated at the tissue level using subcutaneous and metastatic tumor models in human and murine systems. The results demonstrated that CMD‐BHQ3‐PTL/DOX@RBCM effectively addressed the challenges of specificity and biocompatibility in vivo, significantly inhibiting CSC‐related tumor metastasis. This inhibitory effect is closely associated with the Hippo/YAP1/SOX9 pathway. This study highlights the effectiveness of the pH‐responsive biomimetic nanoparticle system CMD‐BHQ3‐PTL/DOX@RBCm in delivering PTL to tumor sites, with SOX9 and its upstream Hippo/YAP1 pathway playing a critical role in the underlying mechanism.

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Recent Progress in Microenvironment‐Responsive Nanodrug Delivery Systems for the Targeted Treatment of Rheumatoid Arthritis

Liu,

Yang,

Liu

et al. 2024

WIREs Nanomed Nanobiotechnol

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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that often causes joint pain, swelling, and functional impairments. Drug therapy is the main strategy used to alleviate the symptoms of RA; however, drug therapy may have several adverse effects, such as nausea, vomiting, abdominal pain, diarrhea, gastric ulcers, intestinal bleeding, hypertension, hyperglycemia, infection, fatigue, and indigestion. Moreover, long‐term excessive use of drugs may cause liver and kidney dysfunction, as well as thrombocytopenia. Nanodrug delivery systems (NDDSs) can deliver therapeutics to diseased sites with the controlled release of the payload in an abnormal microenvironment, which helps to reduce the side effects of the therapeutics. Abnormalities in the microenvironment, such as a decreased pH, increased expression of matrix metalloproteinases (MMPs), and increased concentrations of reactive oxygen species (ROS), are associated with the progression of RA but also provide an opportunity to achieve microenvironment‐responsive therapeutic release at the RA site. Microenvironment‐responsive NDDSs may overcome the abovementioned disadvantages of RA therapy. Herein, we comprehensively review recent progress in the development of microenvironment‐responsive NDDSs for RA treatment, including pH‐, ROS‐, MMP‐, and multiresponsive NDDSs. Furthermore, the pathological microenvironment is highlighted in detail.

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MMP13-targeted siRNA-loaded micelles for diagnosis and treatment of posttraumatic osteoarthritis

Cited by 6 publications

References 49 publications

Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis

Magnetic Polysaccharide Mesenchymal Stem Cells Exosomes Delivery Microcarriers for Synergistic Therapy of Osteoarthritis

Biomimetic Nano‐delivery of Small‐Molecule Piceatannol Modulates Tumor Stemness and Suppresses Colorectal Cancer Metastasis via Hippo/YAP1/SOX9 Signaling

Recent Progress in Microenvironment‐Responsive Nanodrug Delivery Systems for the Targeted Treatment of Rheumatoid Arthritis

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