Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Theragnostic Nanosomes for Detection and Treatment of Early Osteoarthritis and Cartilage Damage.
Hasty1, Karen A., Cho2, Hongsik, Pinkhassik3, Eugene, Stuart4, John M.
University of Tennessee Health Science Center, VA Medical Center, Memphis, TN
University of Tennessee Health Science Center, Memphis, TN
University of Memphis, Memphis, TN
VA Medical Center, University of Tennessee Health Science Center, Memphis, TN
Osteoarthritis (OA) is a common condition with few preventive therapies. One obstacle to developing therapies is a reliable method of detecting and measuring progression in the early stages of disease when intervention may prove more beneficial. This application uses fluorescent, targeted nanosomes (200 nm liposomes) developed as a theragnostic delivery system. The nanosomes incorporate a monoclonal antibody (Mab) to native type II collagen (CII) and a near infrared emitting fluorescent dye (NIF) that can be quantitatively visualized in vivo. CII in normal cartilage is not available for binding and is only unmasked when the surface of the cartilage is damaged. We show targeted nanosomes selectively bind exposed CII and can be quantitated using an external imaging system in both inflammatory and degenerative arthritis.
Animal All animal studies were approved IACUC protocols at the University of Tennessee Center for the Health Sciences. Dunkin-Hartley guinea pigs ranging in age 324 month were obtained from The Jackson Laboratory. To induce inflammatory arthritis in mice, DBA/1J mice were immunized with CII in complete Freund's adjuvant and observed until the onset of inflammation. Two months after inflammation subsided, mice were injected with NIF-MabCII nanosomes or control NIF-MabCon nanosomes.
In vivo imaging was done at 24 hours post-injection using a Lumina II, In Vivo Imaging System (IVIS), (Caliper Life Sciences, MA) with an Indocyanine Green (ICG) Filter set (excitation 710760nm, emission 810875 nm). With imaging, older guinea pigs showed a significant difference between intraarticularly injected nanosomes with MabCII and those bound to control Mab. The NIF-MabCII showed a high degree of binding and exhibited fluorescence corresponding to joint degradation. This binding is proportional to the histopathological stage of cartilage damage in the joint. The administered nanosomes conjugated to a control antibody showed minimal binding. A minimal amount of binding was also observed in the young guinea pig for both control and experimental nanosomes. IVIS imaging of the dissected joint tissue surrounding the joint in both young and old samples showed no soft tissue fluorescence. Dissection showed binding of the NIF-MabCII-nanosomes was principally to the medial condyle. Histopathology of the joint showed the young joint had limited degradation while older joints displayed osteoarthritis with characteristic cartilage damage. IVIS imaging showed that nanosomes labeled with NIF-MabCII targeted directly to knee joints of animals that had previously shown evidence of CIA, when injected intravascularly or intraarticularly. Controls were negative.
Specific binding of nanosomes conjugated to type II collagen antibodies in joints with spontaneous OA and those damaged by CIA was seen. Collected data indicated the amount of nanosome binding is proportional to the level of cartilage damage. Adding drugs or cytokines inside the nanosomes may offer a method for diagnosis and treatmetn of early OA before clinical presentation of the disease.
Funded by a VA Merit Award (KAH) and funds from the CTSI at UTHSC.
To cite this abstract, please use the following information:
Hasty, Karen A., Cho, Hongsik, Pinkhassik, Eugene, Stuart, John M.; Theragnostic Nanosomes for Detection and Treatment of Early Osteoarthritis and Cartilage Damage. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1798