Comprehensive spectral endoscopy of topically applied SERS nanoparticles in the rat esophagus.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang YW
PROVIDER: S-EPMC4230873 | biostudies-other | 2014 Sep
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Multiplexed surface-enhanced Raman scattering (SERS) nanoparticles (NPs) offer the potential for rapid molecular phenotyping of tissues, thereby enabling accurate disease detection as well as patient stratification to guide personalized therapies or to monitor treatment outcomes. The clinical success of molecular diagnostics based on SERS NPs would be facilitated by the ability to accurately identify tissue biomarkers under time-constrained staining and detection conditions with a portable device. In vitro, ex vivo and in vivo experiments were performed to optimize the technology and protocols for the rapid detection (0.1-s integration time) of multiple cell-surface biomarkers with a miniature fiber-optic spectral-detection probe following a brief (5 min) topical application of SERS NPs on tissues. Furthermore, we demonstrate that the simultaneous detection and ratiometric quantification of targeted and nontargeted NPs allows for an unambiguous assessment of molecular expression that is insensitive to nonspecific variations in NP concentrations.
| S-EPMC4103661 | biostudies-literature
Project description:Intraoperative identification of carcinoma at lumpectomy margins would enable reduced re-excision rates, which are currently as high as 20% to 50%. Although imaging of disease-associated biomarkers can identify malignancies with high specificity, multiplexed imaging of such biomarkers is necessary to detect molecularly heterogeneous carcinomas with high sensitivity. We have developed a Raman-encoded molecular imaging (REMI) technique in which targeted nanoparticles are topically applied on excised tissues to enable rapid visualization of a multiplexed panel of cell surface biomarkers at surgical margin surfaces. A first-ever clinical study was performed in which 57 fresh specimens were imaged with REMI to simultaneously quantify the expression of four biomarkers HER2, ER, EGFR, and CD44. Combined detection of these biomarkers enabled REMI to achieve 89.3% sensitivity and 92.1% specificity for the detection of breast carcinoma. These results highlight the sensitivity and specificity of REMI to detect biomarkers in freshly resected tissue, which has the potential to reduce the rate of re-excision procedures in cancer patients. Cancer Res; 77(16); 4506-16. ©2017 AACR.
| S-EPMC5559330 | biostudies-literature
Project description:There is a need to image excised tissues during tumor-resection procedures in order to identify residual tumors at the margins and to guide their complete removal. The imaging of dysregulated cell-surface receptors is a potential means of identifying the presence of diseases with high sensitivity and specificity. However, due to heterogeneities in the expression of protein biomarkers in tumors, molecular-imaging technologies should ideally be capable of visualizing a multiplexed panel of cancer biomarkers. Here, we demonstrate that the topical application and quantification of a multiplexed cocktail of receptor-targeted surface-enhanced Raman scattering (SERS) nanoparticles (NPs) enables rapid quantitative molecular phenotyping (QMP) of the surface of freshly excised tissues to determine the presence of disease. In order to mitigate the ambiguity due to nonspecific sources of contrast such as off-target binding or uneven delivery, a ratiometric method is employed to quantify the specific vs. nonspecific binding of the multiplexed NPs. Validation experiments with human tumor cell lines, fresh human tumor xenografts in mice, and fresh human breast specimens demonstrate that QMP imaging of excised tissues agrees with flow cytometry and immunohistochemistry, and that this technique may be achieved in less than 15?minutes for potential intraoperative use in guiding breast-conserving surgeries.
| S-EPMC4754709 | biostudies-other
Project description:Early detection of esophageal neoplasia enables curative endoscopic therapy, but the current diagnostic standard of care has low sensitivity because early neoplasia is often inconspicuous with conventional white-light endoscopy. Here, we hypothesized that spectral endoscopy could enhance contrast for neoplasia in surveillance of patients with Barrett's esophagus. A custom spectral endoscope was deployed in a pilot clinical study of 20 patients to capture 715 in vivo tissue spectra matched with gold standard diagnosis from histopathology. Spectral endoscopy was sensitive to changes in neovascularization during the progression of disease; both non-dysplastic and neoplastic Barrett's esophagus showed higher blood volume relative to healthy squamous tissue (P = 0.001 and 0.02, respectively), and vessel radius appeared larger in neoplasia relative to non-dysplastic Barrett's esophagus (P = 0.06). We further developed a deep learning algorithm capable of classifying spectra of neoplasia versus non-dysplastic Barrett's esophagus with high accuracy (84.8% accuracy, 83.7% sensitivity, 85.5% specificity, 78.3% positive predictive value, and 89.4% negative predictive value). Exploiting the newly acquired library of labeled spectra to model custom color filter sets identified a potential 12-fold enhancement in contrast between neoplasia and non-dysplastic Barrett's esophagus using application-specific color filters compared with standard-of-care white-light imaging (perceptible color difference = 32.4 and 2.7, respectively). This work demonstrates the potential of endoscopic spectral imaging to extract vascular properties in Barrett's esophagus, to classify disease stages using deep learning, and to enable high-contrast endoscopy. SIGNIFICANCE: The results of this pilot first-in-human clinical trial demonstrate the potential of spectral endoscopy to reveal disease-associated vascular changes and to provide high-contrast delineation of neoplasia in the esophagus. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3415/F1.large.jpg.
| S-EPMC7611389 | biostudies-literature
Project description:Previous studies have shown that functionalized nanoparticles (NPs) topically applied on fresh tissues are able to rapidly target cell-surface protein biomarkers of cancer. Furthermore, studies have shown that a paired-agent approach, in which an untargeted NP is co-administered with a panel of targeted NPs, controls for the nonspecific behavior of the NPs, enabling quantitative imaging of biomarker expression. However, given the complexities in nonspecific accumulation, diffusion, and chemical binding of targeted NPs in tissues, studies are needed to better understand these processes at the microscopic scale. Here, fresh tissues were stained with a paired-agent approach, frozen, and sectioned to image the depth-dependent accumulation of targeted and untargeted NPs. The ratio of targeted-to-untargeted NP concentrations-a parameter used to distinguish between tumor and benign tissues-was found to diminish with increasing NP diffusion depths due to nonspecific accumulation and poor washout. It was then hypothesized and experimentally demonstrated that larger NPs would exhibit less diffusion below tissue surfaces, enabling higher targeted-to-untargeted NP ratios. In summary, these methods and investigations have enabled the design of NP agents with improved sensitivity and contrast for rapid molecular imaging of fresh tissues.
| S-EPMC5903997 | biostudies-literature
Project description:Nanoparticle spectroscopic tags based on surface enhanced Raman scattering (SERS) are playing an increasingly important role in bioassay and imaging applications. The ability to rapidly characterize large populations of such tags spectroscopically in a high-throughput flow-based platform will open new areas for their application and provide new tools for advancing their development. We demonstrate here a high-resolution spectral flow cytometer capable of acquiring Raman spectra of individual SERS-tags at flow rates of hundreds of particles per second, while maintaining the spectral resolution required to make full use of the detailed information encoded in the Raman signature for advanced multiplexing needs. The approach allows multiple optical parameters to be acquired simultaneously over thousands of individual nanoparticle tags. Characteristics such as tag size, brightness, and spectral uniformity are correlated on a per-particle basis. The tags evaluated here display highly uniform spectral signatures, but with greater variability in brightness. Subpopulations in the SERS response, not apparent in ensemble measurements, are also shown to exist. Relating tag variability to synthesis parameters makes flow-based spectral characterization a powerful tool for advancing particle development through its ability to provide rapid feedback on strategies aimed at constraining desired tag properties. Evidence for single-tag signal saturation at high excitation power densities is also shown, suggesting a role for high-throughput investigation of fundamental properties of the SERS tags as well.
| S-EPMC2861152 | biostudies-literature
Project description:We developed an inhibitory peptide that specifically acts against mitochondrial ?-calpain (Tat-?CL, 23 amino acid, 2857.37 Da) and protects photoreceptors in retinal dystrophic rats. In the present study, we topically administered Tat-?CL to the eyes of Sprague-Dawley rats for 7 days to determine both the delivery route of the peptide to the posterior segment of the eye and the kinetics after topical application in adult rats. Distribution of the peptide was determined by immunohistochemical analysis, and enzyme-linked immune-absorbent assay was used to quantify the accumulation in the retina. Peptides were prominently detected in both the anterior and posterior segments of the eye at 1 h after the final eye drop application. Immunohistochemically positive reactions were observed in the retina, optic nerve, choroid, sclera and the retrobulbar tissues, even in the posterior portion of the eye. Immunoactivities gradually diminished at 3 and 6 h after the final eye drop. Quantitative estimations of the amount of peptide in the retina were 15.3, 5.8 and 1.0 pg/?g protein at 1, 3 and 6 h after the final instillation, respectively. Current results suggest that while the topically applied Tat-?CL peptide reaches the posterior segment of the retina and the optic nerve, the sufficient concentration (> IC50) is maintained for at least 6 h in the rat retina. Our findings suggest that delivery of topically applied peptide to the posterior segment and optic nerve occurs through the conjunctiva, periocular connective tissue, sclera and optic nerve sheath.
| S-EPMC4479448 | biostudies-literature
Project description:Nanoparticle (NP) contrast agents targeted to cancer biomarkers are increasingly being engineered for the early detection of cancer, guidance of therapy, and monitoring of response. There have been recent efforts to topically apply biomarker-targeted NPs on tissue surfaces to image the expression of cell-surface receptors over large surface areas as a means of evaluating tumor margins to guide wide local excision surgeries. However, diffusion and nonspecific binding of the NPs present challenges for relating NP retention on the tissue surface with the expression of cancer cell receptors. Paired-agent methods that employ a secondary 'control' NP to account for these nonspecific effects can improve cancer detection. Yet these paired-agent methods introduce multidimensional complexity (with tissue staining, rinsing, imaging, and data analysis protocols all being subject to alteration), and could be greatly simplified with accurate, predictive in silico models of NP binding and diffusion. Here, we outline and validate such a model to predict the diffusion, as well as specific and nonspecific binding, of targeted and control NPs topically applied on tissue surfaces. In order to inform the model, in vitro experiments were performed to determine relevant NP diffusion and binding rate constants in tissues. The predictive capacity of the model was validated by comparing simulated distributions of various sizes of NPs in comparison with experimental results. The regression of predicted and experimentally measured concentration-depth profiles yielded??<15% error (compared to ~70% error obtained using a previous model of NP diffusion and binding).
| S-EPMC7444409 | biostudies-literature
Project description:(Background): Multi-drug-resistant Klebsiella pneumoniae (MDR-KP) has steadily grown beyond antibiotic control. Wound infection kills many patients each year, due to the entry of multi-drug resistant (MDR) bacterial pathogens into the skin gaps. However, a bacteriophage (phage) is considered to be a potential antibiotic alternative for treating bacterial infections. This research aims at isolating and characterizing a specific phage and evaluate its topical activity against MDR-KP isolated from infected wounds. (Methods): A lytic phage ZCKP8 was isolated by using a clinical isolate KP/15 as a host strain then characterized. Additionally, phage was assessed for its in vitro host range, temperature, ultraviolet (UV), and pH sensitivity. The therapeutic efficiency of phage suspension and a phage-impeded gel vehicle were assessed in vivo against a K. pneumoniae infected wound on a rat model. (Result): The phage produced a clear plaque and was classified as Siphoviridae. The phage inhibited KP/15 growth in vitro in a dose-dependent pattern and it was found to resist high temperature (˂70 °C) and was primarily active at pH 5; moreover, it showed UV stability for 45 min. Phage-treated K. pneumoniae inoculated wounds showed the highest healing efficiency by lowering the infection. The quality of the regenerated skin was evidenced via histological examination compared to the untreated control group. (Conclusions): This research represents the evidence of effective phage therapy against MDR-KP.
| S-EPMC8470685 | biostudies-literature
Project description:An effective wound management strategy needs accurate assessment of wound status throughout the whole healing process. This can be achieved by examining molecular biomarkers including proteins, DNAs, and RNAs. However, existing methods for quantifying these biomarkers such as immunohistochemistry and quantitative polymerase chain reaction are usually laborious, resource-intensive, and disruptive. This article reports the development and utilization of mRNA nanosensors (i.e., NanoFlare) that are topically applied on cutaneous wounds to reveal the healing status through targeted and semi-quantitative examination of the mRNA biomarkers in skin cells. In 2D and 3D in vitro models, the efficacy and efficiency of these nanosensors are demonstrated in revealing the dynamic changes of mRNA biomarkers for different stages of wound development. In mouse models, this platform permits the tracking and identification of wound healing stages and a normal and diabetic wound healing process by wound healing index in real time.
| S-EPMC9218655 | biostudies-literature