1. Tumor-targeted small molecule for dual-modal imaging-guided phototherapy upon near-infrared excitation
- Author
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Lintao Cai, Lihua Zhou, Zhihong Sun, Zhang Jiali, Guanjun Deng, Wenjun Li, Meng Xiaoqing, and Ping Gong
- Subjects
Tumor microenvironment ,Fluorescence-lifetime imaging microscopy ,Materials science ,Fluorophore ,Biomedical Engineering ,Nanotechnology ,02 engineering and technology ,General Chemistry ,General Medicine ,Photothermal therapy ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Fluorescence ,0104 chemical sciences ,chemistry.chemical_compound ,Nuclear magnetic resonance ,chemistry ,In vivo ,General Materials Science ,Cyanine ,0210 nano-technology ,Molecular probe - Abstract
Near-infrared (NIR) organic dyes have received increasing attention in recent years as diagnostic and therapeutic agents in the field of tumor research. In this study, IR-822, a near-infrared fluorescence (NIRF) heptamethine cyanine dye, was chosen as a fluorophore due to its high extinction coefficients, and native preferential tumor accumulation property. To enhance its specificity in tumor imaging, N1-(pyridin-4-ylmethyl)ethane-1,2-diamine (PY) was conjugated to IR-822 as a pH-sensing receptor, forming a fluorophore–spacer–receptor molecular probe (IR-PY) that can modulate the fluorescence emission intensity through a fast photoinduced electron-transfer process, which allowed the probe to “switch on” significantly in an acidic tumor microenvironment and which realized enhanced NIRF imaging in vivo. Having a strong NIR absorption at 600–850 nm, this small-molecule IR-PY showed not only high spatial resolution photoacoustic (PA) imaging in mice, but also effective tumor photothermal ablation in vivo. After photothermal therapy (PTT) with IR-PY under NIR 808 nm laser irradiation, the mice exhibited remarkable ablation with no tumor recurrence after treatment. Therefore, a single smart small-molecule probe IR-PY has been designed, synthesized and verified as an “all in one” multifunctional agent, including pH sensitivity, tumor targeting, “switch-on” near-infrared fluorescence imaging, high-spatial-resolution PA imaging and efficient near-infrared photothermal therapy, which is promising for clinical application in NIRF/PA dual-modal imaging-guided cancer diagnosis and treatment.
- Published
- 2017