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Updated: May 23, 2026
In Vivo Optical Imaging of Brain Tumors and Arthritis Using Fluorescent SapC-DOPS Nanovesicles
Published on: May 2, 2014
Saposin C coupled lipid nanovesicles specifically target arthritic mouse joints for optical imaging of disease
Xiaoyang Qi1, Matthew J Flick, Malinda Frederick
1Division of Hematology-Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Abstract:
Rheumatoid arthritis is a chronic inflammatory disease affecting approximately 1% of the population and is characterized by cartilage and bone destruction ultimately leading to loss of joint function. Early detection and intervention of disease provides the best hope for successful treatment and preservation of joint mobility and function. Reliable and non-invasive techniques that accurately measure arthritic disease onset and progression are lacking. We recently developed a novel agent, SapC-DOPS, which is composed of the membrane-associated lysosomal protein saposin C (SapC) incorporated into 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) lipid nanovesicles. SapC-DOPS has a high fusogenic affinity for phosphatidylserine-enriched microdomains on surfaces of target cell membranes. Incorporation of a far-red fluorophore, CellVue Maroon (CVM), into the nanovesicles allows for in vivo non-invasive visualization of the agent in targeted tissue. Given that phosphatidylserine is present only on the inner leaflet of healthy plasma membranes but is "flipped" to the outer leaflet upon cell damage, we hypothesized that SapC-DOPS would target tissue damage associated with inflammatory arthritis due to local surface-exposure of phosphatidylserine. Optical imaging with SapC-DOPS-CVM in two distinct models of arthritis, serum-transfer arthritis (e.g., K/BxN) and collagen-induced arthritis (CIA) revealed robust SapC-DOPS-CVM specific localization to arthritic paws and joints in live animals. Importantly, intensity of localized fluorescent signal correlated with macroscopic arthritic disease severity and increased with disease progression. Flow cytometry of cells extracted from arthritic joints demonstrated that SapC-DOPS-CVM localized to an average of 7-8% of total joint cells and primarily to CD11b+Gr-1+ cells. Results from the current studies strongly support the application of SapC-DOPS-CVM for advanced clinical and research applications including: detecting early arthritis onset, assessing disease progression real-time in live subjects, and providing novel information regarding cell types that may mediate arthritis progression within joints.
Insights
A new imaging agent, SapC-DOPS-CVM, effectively targets and visualizes joint damage in arthritis models. This breakthrough aids in early detection and real-time monitoring of rheumatoid arthritis progression.
Area of Science:
- Biomedical imaging
- Nanotechnology
- Rheumatology
Background:
- Rheumatoid arthritis is a chronic inflammatory disease causing joint destruction and functional loss.
- Current diagnostic methods lack non-invasive techniques for early detection and progression monitoring.
- Phosphatidylserine exposure on damaged cells presents a potential biomarker for arthritis.
Purpose of the Study:
- To develop and evaluate a novel imaging agent, SapC-DOPS-CVM, for non-invasive detection of arthritis.
- To assess the agent's ability to target and visualize arthritic joint damage in vivo.
- To correlate imaging signal intensity with disease severity and progression.
Main Methods:
- SapC-DOPS nanovesicles incorporating CellVue Maroon (CVM) fluorophore were synthesized.
- The agent was tested in serum-transfer and collagen-induced arthritis mouse models.
- In vivo optical imaging, macroscopic scoring, and flow cytometry were employed.
Main Results:
- SapC-DOPS-CVM demonstrated specific localization to arthritic paws and joints in live animals.
- Fluorescent signal intensity correlated with macroscopic arthritis severity and disease progression.
- Flow cytometry revealed localization primarily to CD11b+Gr-1+ cells within affected joints.
Conclusions:
- SapC-DOPS-CVM is a promising tool for non-invasive, real-time detection and monitoring of arthritis.
- The agent facilitates early diagnosis and assessment of disease progression.
- Findings provide insights into cellular mechanisms of arthritis progression within joints.
