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.cancer imaging | fluorescence-guided surgery | M13 bacteriophage I n clinical oncology, in vivo fluorescence imaging has emerged as a valuable tool for improving diagnosis, staging tumors, monitoring response to therapy, and detecting recurrent or residual disease. Compared with existing imaging modalities, fluorescence imaging offers a low-cost, portable, and safe alternative (i.e., nonionizing radiation), with key advantages including realtime imaging, superior resolution, and high specificity for small tumor nodules during diagnostic and intraoperative surgical procedures (1, 2). Although efforts have focused on using visible and short near-infrared (NIR1, 650-900 nm) wavelength fluorescent dyes as contrast agents for delineating tumor margins in both preclinical cancer models (2, 3) and human patients (4), these agents are suboptimal for noninvasive, reflectance-based imaging due to limited penetration depth (3-5 mm) and high tissue autofluorescence. During intraoperative surgery, these dyes may additionally undergo photobleaching, thereby reducing the ability of the surgeon to readily locate and resect tumors. Alternative approaches to specifically permit noninvasive imaging and limited photobleaching would be highly desirable for diagnostic and surgical applications.Single-walled carbon nanotubes (SWNTs) hold great promise as fluorescence imaging agents due to the large interband difference between their excitation and emission wavelengths, resulting in minimal spectral overlap and tissue autofluorescence. In particular, the low tissue autofluorescence observed with SWNTs greatly enhances target-to-background ratios (TBRs) necessary for improved detection of small tumor nodules in confined anatomic regions. SWNT emission at longer wavelengths in the near-infrared second window (NIR2, 950-1,400 nm) results in less optical scattering and deeper tissue p...

SUMMARY Analysis of cancer-derived extracellular vesicles (EVs) in biofluids potentially provides a source of disease biomarkers. At present there is no procedure to systematically identify which antigens should be targeted to differentiate cancer-derived from normal host cell-derived EVs. Here, we propose a computational framework that integrates information about membrane proteins in tumors and normal tissues from databases: UniProt, The Cancer Genome Atlas, the Genotype-Tissue Expression Project, and the Human Protein Atlas. We developed two methods to assess capture of EVs from specific cell types. (1) We used palmitoylated fluorescent protein (palmtdTomato) to label tumor-derived EVs. Beads displaying antibodies of interest were incubated with conditioned medium from palmtdTomato-expressing cells. Bound EVs were quantified using flow cytometry. (2) We also showed that membrane-bound Gaussia luciferase allows the detection of cancer-derived EVs in blood of tumor-bearing animals. Our analytical and validation platform should be applicable to identify antigens on EVs from any tumor type.

Intraperitoneal (IP) chemotherapy for ovarian cancer treatment prolongs overall survival by 16 months compared to intravenous chemotherapy but is not widely practiced due to catheter-related complications and complexity of administration. An implantable, nonresorbable IP microdevice was used to release chemotherapeutic agent at a constant rate of approximately 1.3 µg/hour in vitro and 1.0 µg/hour in vivo. Studies conducted in two orthotopic murine models bearing human xenografts (SKOV3 and UCI101) demonstrate that continuous dosing reduces tumor burden to the same extent as weekly IP bolus drug injections. Treatment-induced toxicity was quantified via body weight loss and complete blood count. The microdevice resulted in significantly less toxicity than IP bolus injections, despite administration of higher cumulative doses (total area under the concentration-time curve of 3,049 ng-day/mL with the microdevice vs. 2,118 ng-day/mL with IP bolus injections). This preclinical study supports the concept that reduced toxicity with similar efficacy outcomes can be achieved by continuous dosing in ovarian cancer patients currently treated with IP therapy.