International journal of nanomedicine · 2026
PEG-NH2-Modified Gold Nanoparticle Deliver miRNA-140 for Effective Treatment of Osteoarthritis.
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Luo Xiangping, Jiang Xiaochun, Kang Zheng
Аннотация
BACKGROUND: Osteoarthritis is a prevalent disease that causes pain and disability in older adults. MicroRNA-140 (miR-140) emerges as a promising therapeutic agent as it suppresses cartilage-degrading enzymes (eg, ADAMTS5, MMPs). However, its clinical translation is limited by rapid intra-articular degradation and poor chondrocyte penetration. The purpose of this experiment was to construct a nanocarrier for delivering miR-140 into chondrocytes, and to detect its delivery efficiency and biological effects.
METHODS: We engineered polyethylene glycol-aminated gold nanoparticles (AuNPs-PEG-NH2) for miR-140 delivery. The efficiency of AuNPs-PEG-NH2-mediated miR-140-5p (AuNPs-miR-140) delivery was assessed by fluorescence microscopy and flow cytometry. The biological function of AuNPs-miR-140 complexes was detected by quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, and enzyme-linked immunosorbent assay. The effect of AuNPs-miR-140 in attenuating osteoarthritis progression was tested in a mouse model.
RESULTS: Fluorescence microscopy and flow cytometry revealed efficient delivery of miR-140-5p into ATDC5 cells by AuNPs-PEG-NH2. RT-qPCR analysis demonstrated a controlled sustained release of miR-140-5p from the nanocarriers, maintaining elevated miR-140-5p levels for 14 days. In vitro, AuNPs-miR-140 significantly suppressed catabolic factors (MMP-13 and ADAMTS5; p<0.01) and upregulated anabolic markers (COL2 and ACAN; p<0.01) in IL-1β-stimulated chondrocytes. Consistent with these findings, in vivo studies showed that AuNPs-miR-140 significantly attenuated cartilage degradation in mice with osteoarthritis, and preserved cartilage structural integrity.
CONCLUSION: AuNPs-PEG-NH2 is an efficient intra-articular miRNA delivery platform that successfully overcame the critical limitations of free miRNA therapy. This system effectively restored cartilage homeostasis and delayed osteoarthritis progression by prolonging miR-140 bioactivity and promoting chondrocyte uptake.
METHODS: We engineered polyethylene glycol-aminated gold nanoparticles (AuNPs-PEG-NH2) for miR-140 delivery. The efficiency of AuNPs-PEG-NH2-mediated miR-140-5p (AuNPs-miR-140) delivery was assessed by fluorescence microscopy and flow cytometry. The biological function of AuNPs-miR-140 complexes was detected by quantitative real-time polymerase chain reaction (RT-qPCR), Western blot, and enzyme-linked immunosorbent assay. The effect of AuNPs-miR-140 in attenuating osteoarthritis progression was tested in a mouse model.
RESULTS: Fluorescence microscopy and flow cytometry revealed efficient delivery of miR-140-5p into ATDC5 cells by AuNPs-PEG-NH2. RT-qPCR analysis demonstrated a controlled sustained release of miR-140-5p from the nanocarriers, maintaining elevated miR-140-5p levels for 14 days. In vitro, AuNPs-miR-140 significantly suppressed catabolic factors (MMP-13 and ADAMTS5; p<0.01) and upregulated anabolic markers (COL2 and ACAN; p<0.01) in IL-1β-stimulated chondrocytes. Consistent with these findings, in vivo studies showed that AuNPs-miR-140 significantly attenuated cartilage degradation in mice with osteoarthritis, and preserved cartilage structural integrity.
CONCLUSION: AuNPs-PEG-NH2 is an efficient intra-articular miRNA delivery platform that successfully overcame the critical limitations of free miRNA therapy. This system effectively restored cartilage homeostasis and delayed osteoarthritis progression by prolonging miR-140 bioactivity and promoting chondrocyte uptake.