期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：38
页码：13948-13953
DOI：10.1073/pnas.1400821111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceEarly detection of cancer positively impacts diagnosis and treatment, ultimately improving patient survival. Using fluorescence imaging offers the promise of safe, noninvasive detection with excellent resolution and guides surgical removal of tumors to improve patient outcomes. However, the success of current optical probes is limited due to high background from tissue autofluorescence, poor penetration depth, and inherently low signal stability. Here, we engineered M13 bacteriophage to stabilize single-walled carbon nanotubes for selective, targeted imaging of ovarian tumors. These nanoprobes fluoresce at longer near-infrared wavelengths than current probes, thereby improving noninvasive detection of small, deep tumors and guidance for surgical removal of submillimeter tumors. This material-based approach may be attractive to guide surgical interventions where deep tissue molecular imaging is informative. 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.
关键词：cancer imaging ; fluorescence-guided surgery ; M13 bacteriophage
