Nanoparticles Passive Targeting Allows Optical Imaging of Bone Diseases

TL;DR

This study introduces a novel optical imaging method using nanoparticles for non-invasive, radiation-free diagnosis of bone diseases, capable of long-term monitoring and early detection of inflammation and structural abnormalities.

Contribution

The paper presents a passive targeting nanoparticle approach combined with NIR-II optical imaging for effective, long-term bone disease diagnosis and early inflammation detection.

Findings

Effective passive targeting of nanoparticles into bone marrow.

Long-term imaging capability over two months.

Detection of early-stage inflammation and structural bone changes.

Abstract

Bone health related skeletal disorders are commonly diagnosed by X-ray imaging, but the radiation limits its use. Light excitation and optical imaging through the near-infrared-II window (NIR-II, 1000-1700 nm) can penetrate deep tissues without radiation risk, but the targeting of contrast agent is non-specific. Here, we report that lanthanide-doped nanocrystals can be passively transported by endothelial cells and macrophages from the blood vessels into bone marrow microenvironment. We found that this passive targeting scheme can be effective for longer than two months. We therefore developed an intravital 3D and high-resolution planar imaging instrumentation for bone disease diagnosis. We demonstrated the regular monitoring of 1 mm bone defects for over 10 days, with resolution similar to X-ray imaging result, but more flexible use in prognosis. Moreover, the passive targeting can be used to reveal the early onset inflammation at the joints as the synovitis in the early stage of rheumatoid arthritis. Furthermore, the proposed method is comparable to {\mu}CT in recognizing symptoms of osteoarthritis, including the mild hyperostosis in femur which is ~100 {\mu}m thicker than normal, and the growth of millimeter-scale osteophyte in the knee joint, which further proves the power and universality of our approach in diagnosis of bone diseases