Hongsik Cho,1,2,* Byoung Ju Kim,3,4,* Sang-Hyug Park,5 Karen A Hasty,1,2 Byoung-Hyun Min3,4,6 1Department of Orthopaedic Surgery and Biomedical Engineering, University of Tennessee Health Science Center–Campbell Clinic, 2Veterans Affairs Medical Center, Memphis, TN, USA; 3Department of Molecular Science and Technology, Ajou University, 4Cell Therapy Center, Ajou University Hospital, Suwon, 5Department of Biomedical Engineering, Pukyong National University, Nam-Gu, Busan, 6Department of Orthopedic Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea *These authors contributed equally to this work Background: Early stage osteoarthritis (OA) is clinically asymptomatic due to the avascular and the aneural nature of the cartilage tissue. Nevertheless, early detection of cartilage tissue is critical in order to impede the progression of OA. Hence, in order to develop effective preventive therapy for OA, diagnosis in the early stages is necessary.Methods: To achieve this goal, we have developed targeted, fluorescent nanosomes conjugated with monoclonal anti-type II collagen antibodies (MabCII) for diagnosis of early OA. The MabCII-coated nanosomes (targeted-nanosomes) bind to the damaged cartilage explants in vitro and in vivo in an OA mouse model that mimics early stage OA. The OA mouse model was induced by destabilization of the medial meniscus (DMM) in 9-10 weeks old C57Bl/6 mice.Results: The targeted-nanosomes enhanced the binding specificity to the cartilage tissue according to the severity of damage.Conclusion: We show that MabCII-nanosomes can precisely detect early stage OA in the DMM mouse model. Thus, MabCII-nanosomes have the potential to be used as a non-invasive method for diagnosing the early osteoarthritic lesions. Keywords: osteoarthritis, nanosome, diagnosis, OA score, destabilization of the medial meniscus, matrix metalloproteinases, monoclonal anti-type II collagen antibody