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用抗体功能化的硫酸铜纳米粒子将衰老的软骨转化为促软骨形成的微环境，用于高效的骨关节炎治疗。

Conversion of senescent cartilage into a pro-chondrogenic microenvironment with antibody-functionalized copper sulfate nanoparticles for efficient osteoarthritis therapy.

机构信息

Department of Orthopedic Surgery, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.

The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.

出版信息

J Nanobiotechnology. 2023 Aug 8;21(1):258. doi: 10.1186/s12951-023-02036-5.

DOI:10.1186/s12951-023-02036-5
PMID:37550685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10408088/
Abstract

The development of osteoarthritis (OA) correlates with the expansion of senescent cells in cartilage, which contributes to an inflammatory microenvironment that accelerates matrix degradation and hampers cartilage generation. To address OA, we synthesized small copper sulfide nanoparticles functionalized with anti-beta-2-microglobulin antibodies (B2M-CuS NPs) that catalyze the formation of toxic •OH from HO via peroxidase-like activity. These B2M-CuS NPs are specifically targeted to induce apoptosis in senescent chondrocytes while showing no toxicity toward normal chondrocytes. Furthermore, B2M-CuS NPs enhance the chondrogenesis of normal chondrocytes. Thus, B2M-CuS NPs can effectively treat OA by clearing senescent chondrocytes and promoting cartilage regeneration after intra-articular injection into the knee joints of surgery-induced OA mice. This study uses smart nanomaterials to treat OA with a synergistic strategy that both remodels senescent cartilage and creates a pro-chondrogenic microenvironment.

摘要

骨关节炎 (OA) 的发展与软骨中衰老细胞的扩张相关，这导致了炎症微环境，加速了基质降解并阻碍了软骨生成。为了解决 OA 问题，我们合成了一种经过抗β-2-微球蛋白抗体（B2M-CuS NPs）功能化的小硫化铜纳米颗粒，该纳米颗粒通过过氧化物酶样活性将 HO 催化形成有毒的•OH。这些 B2M-CuS NPs 被特异性靶向以诱导衰老软骨细胞凋亡，同时对正常软骨细胞没有毒性。此外，B2M-CuS NPs 还能增强正常软骨细胞的软骨生成。因此，B2M-CuS NPs 通过清除衰老的软骨细胞并在手术诱导的 OA 小鼠膝关节内关节注射后促进软骨再生，可有效治疗 OA。本研究使用智能纳米材料通过协同策略治疗 OA，既能重塑衰老的软骨又能创造有利于软骨生成的微环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/47febe57c662/12951_2023_2036_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/57b3be7ba8f3/12951_2023_2036_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/c7084a589cc1/12951_2023_2036_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/e80a3fd5b3e9/12951_2023_2036_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/5689a7b69080/12951_2023_2036_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/3ab6662b0b4d/12951_2023_2036_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/5b5401584caf/12951_2023_2036_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/ffc9284e9d77/12951_2023_2036_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/47febe57c662/12951_2023_2036_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/57b3be7ba8f3/12951_2023_2036_Sch1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/c7084a589cc1/12951_2023_2036_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/e80a3fd5b3e9/12951_2023_2036_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/5689a7b69080/12951_2023_2036_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/3ab6662b0b4d/12951_2023_2036_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/5b5401584caf/12951_2023_2036_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/ffc9284e9d77/12951_2023_2036_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/10408088/47febe57c662/12951_2023_2036_Fig8_HTML.jpg

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Targeted therapy for knee osteoarthritis: From basic to clinics.

Medicine (Baltimore). 2025-8-15

[2]
Elemental Influence: The Emerging Role of Zinc, Copper, and Selenium in Osteoarthritis.

Nutrients. 2025-6-21

[3]
Enhancing Cartilage Repair in Osteoarthritis Using Platelet Lysates and Arthroscopic Microfracture.

Drug Des Devel Ther. 2025-5-13

[4]
Inhibiting synovial inflammation and promoting cartilage repair in rheumatoid arthritis using a matrix metalloproteinase-binding hydrogel.

Mater Today Bio. 2025-4-23

[5]
Nanomaterial-Based Drug Delivery Systems Targeting Functional Cells for Osteoarthritis Treatment: Mechanisms, Challenges and Future Prospects.

Int J Nanomedicine. 2025-4-25

[6]
Advances in copper-containing biomaterials for managing bone-related diseases.

Regen Biomater. 2025-3-18

[7]
Harnessing the potential of hyaluronic acid methacrylate (HAMA) hydrogel for clinical applications in orthopaedic diseases.

J Orthop Translat. 2025-1-8

[8]
Identification of key biomarkers related to fibrocartilage chondrocytes for osteoarthritis based on bulk, single-cell transcriptomic data.

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[9]
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[10]
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本文引用的文献

[1]
Nanomechanics of Aggrecan: A New Perspective on Cartilage Biomechanics, Disease and Regeneration.

Adv Exp Med Biol. 2023

[2]
The Mechanism and Role of ADAMTS Protein Family in Osteoarthritis.

Biomolecules. 2022-7-8

[3]
Label-free fluorescence detection of hydrogen peroxide and glucose based on the Ni-MOF nanozyme-induced self-ligand emission.

Mikrochim Acta. 2022-5-16

[4]
Enhanced osteoarthritis therapy by nanoengineered mesenchymal stem cells using biomimetic CuS nanoparticles loaded with plasmid DNA encoding TGF-β1.

Bioact Mater. 2022-5-2

[5]
Highly effective rheumatoid arthritis therapy by peptide-promoted nanomodification of mesenchymal stem cells.

Biomaterials. 2022-4

[6]
Hierarchical functional nanoparticles boost osteoarthritis therapy by utilizing joint-resident mesenchymal stem cells.

J Nanobiotechnology. 2022-2-19

[7]
Immunotherapy for Tumor Metastasis by Artificial Antigen-Presenting Cells via Targeted Microenvironment Regulation and T-Cell Activation.

ACS Appl Mater Interfaces. 2021-12-1

[8]
Blood and urine biomarkers in osteoarthritis - an update on cartilage associated type II collagen and aggrecan markers.

Curr Opin Rheumatol. 2022-1-1

[9]
Thymoquinone and Costunolide Induce Apoptosis of Both Proliferative and Doxorubicin-Induced-Senescent Colon and Breast Cancer Cells.

Integr Cancer Ther. 2021

[10]
Catalytic-Enhanced Lactoferrin-Functionalized Au-Bi Se Nanodots for Parkinson's Disease Therapy via Reactive Oxygen Attenuation and Mitochondrial Protection.

Adv Healthc Mater. 2021-7

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