Noninvasive visualization of early osteoarthritic cartilage using targeted nanosomes in a destabilization of the medial meniscus mouse model

Abstract

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.

Intra-articular targeting of nanomaterials for the treatment of osteoarthritis

“…After intravenous injection, these particles migrate into the joint but do not bind to cartilage unless the collagen II network is exposed, namely i n conditions of tissue degradation [91]. Additionally, similar particles were shown via fluorescence to accumulate in the knee in a manner proportional to OA severity in vivo [92].…”

Leveraging Electrostatic Interactions for Drug Delivery to the Joint

“…17,18 Targeting strategies for cartilage have leveraged these unique ECM characteristics, including passive targeting of nanomaterials to cartilage via electrostatic attraction to the anionic cartilage matrix 19,20 and active targeting strategies using binding moieties or agents specific to collagen type II. [21][22][23] Synovial fluid, the viscous non-Newtonian fluid within the joint space, is essential not only for shock absorption and lubrication but also for modulating the transport of various molecules to different tissues of the joint. Synovial fluid is a protein-rich mixture of plasma and hyaluronan synthesized by type B fibroblast-like synoviocytes.…”

Biomaterial strategies for improved intra‐articular drug delivery

“…Moreover, targeting cartilage extracellular matrix (ECM) components such as collagen Type II and aggrecan has gained attention as a promising strategy to target damaged areas of the articular cartilage (Figure 3). In fact, monoclonal anti‐Type II collagen antibodies (MabCII) have been used in multiple drug delivery and diagnostics applications 97‐99 . For example, Cho et al demonstrated that liposomes functionalized with a collagen Type II monoclonal antibody are able to bind cartilage tissue proportionally to the severity of the disease in a mice model of OA after systemic administration 99 .…”

“…In fact, monoclonal anti‐Type II collagen antibodies (MabCII) have been used in multiple drug delivery and diagnostics applications 97‐99 . For example, Cho et al demonstrated that liposomes functionalized with a collagen Type II monoclonal antibody are able to bind cartilage tissue proportionally to the severity of the disease in a mice model of OA after systemic administration 99 . Moreover, Bedingfield et al used MabCII‐functionalized polymeric NPs for cartilage‐specific MMP13 siRNA delivery.…”