Ghosh Debadyuti, Bagley Alexander F, Na Young Jeong, Birrer Michael J, Bhatia Sangeeta N, Belcher Angela M
Koch Institute for Integrative Cancer Research, Departments of Materials Science and Engineering.
Koch Institute for Integrative Cancer Research, Biophysics Program, Harvard University, Boston, MA 02115; MD-PhD Program, Harvard Medical School, Boston, MA 02115; and.
Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13948-53. doi: 10.1073/pnas.1400821111. Epub 2014 Sep 11.
Highly sensitive detection of small, deep tumors for early diagnosis and surgical interventions remains a challenge for conventional imaging modalities. Second-window near-infrared light (NIR2, 950-1,400 nm) is promising for in vivo fluorescence imaging due to deep tissue penetration and low tissue autofluorescence. With their intrinsic fluorescence in the NIR2 regime and lack of photobleaching, single-walled carbon nanotubes (SWNTs) are potentially attractive contrast agents to detect tumors. Here, targeted M13 virus-stabilized SWNTs are used to visualize deep, disseminated tumors in vivo. This targeted nanoprobe, which uses M13 to stably display both tumor-targeting peptides and an SWNT imaging probe, demonstrates excellent tumor-to-background uptake and exhibits higher signal-to-noise performance compared with visible and near-infrared (NIR1) dyes for delineating tumor nodules. Detection and excision of tumors by a gynecological surgeon improved with SWNT image guidance and led to the identification of submillimeter tumors. Collectively, these findings demonstrate the promise of targeted SWNT nanoprobes for noninvasive disease monitoring and guided surgery.
对于传统成像方式而言，高灵敏度检测小的深部肿瘤以实现早期诊断和手术干预仍是一项挑战。第二窗口近红外光（NIR2，950 - 1400纳米）由于具有深部组织穿透性和低组织自发荧光特性，在体内荧光成像方面颇具前景。单壁碳纳米管（SWNTs）因其在NIR2区域的固有荧光以及无光漂白特性，是检测肿瘤潜在的有吸引力的造影剂。在此，靶向M13病毒稳定化的SWNTs被用于在体内可视化深部、播散性肿瘤。这种靶向纳米探针利用M13稳定展示肿瘤靶向肽和SWNT成像探针，与用于描绘肿瘤结节的可见光和近红外（NIR1）染料相比，展现出优异的肿瘤与背景摄取比，并具有更高的信噪比性能。妇科外科医生借助SWNT图像引导进行肿瘤检测和切除，得以识别亚毫米级肿瘤。总体而言，这些发现证明了靶向SWNT纳米探针在无创疾病监测和引导手术方面的前景。
