Original Article
Theranostic immunoliposomes for osteoarthritis

https://doi.org/10.1016/j.nano.2013.09.004Get rights and content

Abstract

Although there have been substantial advancements in the treatment of inflammatory arthritis, treatments for osteoarthritis (OA) have lagged and currently are primarily palliative until joints become totally dysfunctional and prosthetic replacement is needed. One obstacle for developing a preventive therapy for OA is the lack of good tools for efficiently diagnosing the disease and monitoring its progression during the early stages when the effect of therapeutic drugs or biologics is most likely to be effective. We have developed near infrared immunoliposomes conjugated with type II collagen antibody for diagnosis and treatment of early OA. These immunoliposomes bind to damaged but not normal cartilage. Utilizing these reagents, we can quantitate exposure of type II collagen during cartilage degradation in individual joints in vivo in a guinea pig. Immunoliposomes could be used to determine the effectiveness of therapeutic interventions in small animals as well as vehicles for localized drug delivery to OA chondrocytes.

From the Clinical Editor

This team of authors have developed near infrared immunoliposomes conjugated with type II collagen antibody for diagnosis and treatment of early OA, with promising results demonstrated in a guinea pig model.

Graphical Abstract

Schematic diagram of antibody targeted immunoliposomes binding onto damaged cartilage. Antibodies to type II collagen are normally blocked from binding to the surface of the articular cartilage. Proteolytic enzymes secreted by resident chondrocytes, synoviocytes or infiltrating leukocytes degrade the surface proteins and allow access of the antibodies to the type II collagen fibrillar network within.

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Section snippets

Animal and in vivo test

Two different age groups (3-5 month and 1-2 years old) of Dunkin-Hartley (DH, osteoarthritic) guinea pigs (n = 12 for each age group) were used in these experiments. The spontaneous model of OA in DH-guinea pigs shares many features of human OA including correlation with obesity, aging and increased severity in weight bearing areas of the articular cartilage.8 100 μl of immunoliposomes that contains near infrared-emitting dye, Xenofluor 750 (0.38 μmol, Caliper Life Science, Hopkinton, MA) and

Characterization of immunoliposomes

After preparation, the size distribution and sample consistency were verified using transmission electron microscopy (TEM; JEM1200EX II, JEOL USA Inc, MA) (Figure 1, C) and dynamic light scattering (DLS) (Figure 1, B). To determine size distribution using TEM, the liposomes were negatively stained by phosphotungstic acid (PTA). In the DLS (Malvern, UK) analysis, the extrusion of multilamellar vesicles through polycarbonate track etched filters with uniform cylindrical 200 nm pores results in

Discussion

In this study, we used the 200 nm size of pendant-type PEG immunoliposomes carrying CII antibodies at the distal ends of the PEG-maleimide chains. This type of liposome has been shown to exhibit higher binding efficiency to target tissues, and this is the type of liposome that this study has employed.20., 21. In addition to the chemical composition, the physical size of the liposome is also a contributory factor to its circulation time.32., 33., 34. Smaller liposomes, nanosomes, ranging in size

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    This work supported with resources and the use facilities at the Veterans Affairs Medical Center (VAMC) at Memphis TN USA. This research was supported by a VA Merit Review award from Department of Veterans Affairs, R21from National Institutes of Health (AR060408) and CTSI from the UTHSC (Karen A. Hasty) and also the Arthritis Foundation Fellowship Award (H. Cho) and the National Science Foundation (CHE-1316680) award (E. Pinkhassik).

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