Ultrahigh Sensitivity Carbon Nanotube Agents for Photoacoustic Molecular Imaging in Living Mice

TLDR

Photoacoustic imaging surpasses optical imaging by providing deeper penetration and higher resolution while preserving strong contrast. The study aims to develop an exogenous photoacoustic contrast agent capable of targeting diseased tissues. The authors engineered a single‑walled carbon nanotube conjugated with indocyanine green and cyclic RGD peptides to bind αvβ3 integrins involved in tumor angiogenesis. In tumor‑bearing mice, the targeted agent produced a 300‑fold higher photoacoustic signal than prior SWNTs, enabling subnanomolar sensitivity and detection of roughly 20 times fewer cancer cells.

Abstract

Photoacoustic imaging is an emerging modality that overcomes to a great extent the resolution and depth limitations of optical imaging while maintaining relatively high-contrast. However, since many diseases will not manifest an endogenous photoacoustic contrast, it is essential to develop exogenous photoacoustic contrast agents that can target diseased tissue(s). Here we present a novel photoacoustic contrast agent, Indocyanine Green dye-enhanced single walled carbon nanotube (SWNT-ICG). We conjugated this contrast agent with cyclic Arg-Gly-Asp (RGD) peptides to molecularly target the αvβ3 integrins, which are associated with tumor angiogenesis. Intravenous administration of this tumor-targeted contrast agent to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. The new contrast agent gave a markedly 300 times higher photoacoustic contrast in living tissues than previously reported SWNTs, leading to subnanomolar sensitivities. Finally, we show that the new contrast agent can detect ∼20 times fewer cancer cells than previously reported SWNTs.