Guiding Brain Tumor Resection Using Surface-Enhanced Raman Scattering Nanoparticles and a Hand-Held Raman Scanner

The current difficulty in visualizing the true extent of malignant brain tumors during surgical resection represents one of the major reasons for the poor prognosis of brain tumor patients. Here, we evaluated the ability of a hand-held Raman scanner, guided by surface-enhanced Raman scattering (SERS) nanoparticles, to identify the microscopic tumor extent in a genetically engineered RCAS/tv-a glioblastoma mouse model. In a simulated intraoperative scenario, we tested both a static Raman imaging device and a mobile, hand-held Raman scanner. We show that SERS image-guided resection is more accurate than resection using white light visualization alone. Both methods complemented each other, and correlation with histology showed that SERS nanoparticles accurately outlined the extent of the tumors. Importantly, the hand-held Raman probe not only allowed near real-time scanning, but also detected additional microscopic foci of cancer in the resection bed that were not seen on static SERS images and would otherwise have been missed. This technology has a strong potential for clinical translation because it uses inert gold-silica SERS nanoparticles and a hand-held Raman scanner that can guide brain tumor resection in the operating room

Plasmonic Control of Radiative Properties of Semiconductor Quantum Dots Coupled to Plasmonic Ring Cavities

In recent years, a lot of effort has been made to achieve controlled delivery of target particles to the hotspots of plasmonic nanoantennas, in order to probe and/or exploit the extremely large field enhancements produced by such structures. While in many cases such high fields are advantageous, there are instances where they should be avoided. In this work, we consider the implications of using the standard nanoantenna geometries when colloidal quantum dots are employed as target entities. We show that in this case, and for various reasons, dimer antennas are not the optimum choice. Plasmonic ring cavities are a better option despite low field enhancements, as they allow collective coupling of many quantum dots in a reproducible and predictable manner. In cases where larger field enhancements are required, or for larger quantum dots, nonconcentric ring-disk cavities can be employed instead

Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

[[abstract]]Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC[[notice]]補正完

Intraoperative Assessment and Photothermal Ablation of the Tumor Margins Using Gold Nanoparticles

Surgical resection is commonly used for therapeutic management of different solid tumors and is regarded as a primary standard of care procedure, but precise localization of tumor margins is a major intraoperative challenge. Herein, a generalized method by optimizing gold nanoparticles for intraoperative detection and photothermal ablation of tumor margins is introduced. These nanoparticles are detectable by highly sensitive surface-enhanced Raman scattering imaging. This non-invasive technique assists in delineating the two surgically challenged tumors in live mice with orthotopic colon or ovarian tumors. Any remaining residual tumors are also ablated by using post-surgical adjuvant photothermaltherapy (aPTT), which results in microscale heat generation due to interaction of these nanoparticles with near-infrared laser. Ablation of these post-operative residual micro-tumors prolongs the survival of mice significantly and delays tumor recurrence by 15 days. To validate clinical translatability of this method, the pharmacokinetics, biodistribution, Raman contrast, aPTT efficiency, and toxicity of these nanoparticles are also investigated. The nanoparticles have long blood circulation time (approximate to 24 h), high tumor accumulation (4.87 +/- 1.73%ID g(-1)) and no toxicity. This high-resolution and sensitive intraoperative approach is versatile and can be potentially used for targeted ablation of residual tumor after resection within different organs.Peer reviewe

Detection of Premalignant Gastrointestinal Lesions Using Surface-Enhanced Resonance Raman Scattering-Nanoparticle Endoscopy

Cancers of the gastrointestinal (GI) tract are among the most frequent and most lethal cancers worldwide. An important reason for this high mortality is that early disease is typically asymptomatic, and patients often present with advanced, incurable disease. Even in high-risk patients who routinely undergo endoscopic screening, lesions can be missed due to their small size or subtle appearance. Thus, current imaging approaches lack the sensitivity and specificity to accurately detect incipient GI tract cancers. Here we report our finding that a single dose of a high-sensitivity surface-enhanced resonance Raman scattering nanoparticle (SERRS-NP) enables reliable detection of precancerous GI lesions in animal models that closely mimic disease development in humans. Some of these animal models have not been used previously to evaluate imaging probes for early cancer detection. The studies were performed using a commercial Raman imaging system, a newly developed mouse Raman endoscope, and finally a clinically applicable Raman endoscope for larger animal studies. We show that this SERRS-NP-based approach enables robust detection of small, premalignant lesions in animal models that faithfully recapitulate human esophageal, gastric, and colorectal tumorigenesis. This method holds promise for much earlier detection of GI cancers than currently possible and could lead therefore to marked reduction of morbidity and mortality of these tumor types