A neutrophil cell membrane-biomimetic nanoplatform based on L-arginine nanoparticles for early osteoarthritis diagnosis and nitric oxide therapyf

摘要

Osteoarthritis(OA)is a common debilitating disease affecting articular joints for which no effective disease-modifying early diagnosis or medical therapy tools are currently available.The inefficient delivery of drugs into inflamed chondrocytes has restricted the development of anti-OA medication.Evidence has shown that inflammatory neutrophils possess the property of targeting inflammation via inflammatory tissue recruiting.Herein,we report neutrophil-cell-membrane-based biomimetic nanoparticles(NM-LANPs@Ru)as an OA theranostic nanoplatform;they act as a NO delivery system,coating neutrophil cell membrane onto the surface of self-assembled PEGylated L-arginine nanoparticles(LANPs)to act as a NO donor and loading a Ru complex to act as a ROS inducer.NM-LANPs@Ru demonstrated the specific targeting of inflamed OA with low toxicity,good NO release,and excellent fluorescence/photoacoustic(FL/PA)imaging properties.We showed that NM-LANPs@Ru exhibited enhanced cellular association in inflamed chondrocyte cells(C28/I2),much higher than NO release from ROS oxidized LA,and it improved the inhibition of the apoptosis of inflamed C28/I2 cells compared with control treatments.In vivo studies demonstrated that NM-LANPs@Ru effectively targeted inflamed OA,based on real-time dual-modal FL/PA imaging,eventually exhibiting its excellent anti-inflammatory activity.Our study may provide a new approach for the early diagnosis and treatment of osteoarthritis using a neutrophil-cell-membrane-based biomimetic nanoplatform for NO or drug delivery.