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1.
Nano Lett ; 19(3): 1409-1417, 2019 03 13.
Artículo en Inglés | MEDLINE | ID: mdl-30433789

RESUMEN

Biological samples such as cells have complex three-dimensional (3D) spatio-molecular profiles and often feature soft and irregular surfaces. Conventional biosensors are based largely on 2D and rigid substrates, which have limited contact area with the entirety of the surface of biological samples making it challenging to obtain 3D spatially resolved spectroscopic information, especially in a label-free manner. Here, we report an ultrathin, flexible skinlike biosensing platform that is capable of conformally wrapping a soft or irregularly shaped 3D biological sample such as a cancer cell or a pollen grain, and therefore enables 3D label-free spatially resolved molecular spectroscopy via surface-enhanced Raman spectroscopy (SERS). Our platform features an ultrathin thermally responsive poly( N-isopropylacrylamide)-graphene-nanoparticle hybrid skin that can be triggered to self-fold and wrap around 3D micro-objects in a conformal manner due to its superior flexibility. We highlight the utility of this 3D biosensing platform by spatially mapping the 3D molecular signatures of a variety of microparticles including silica microspheres, spiky pollen grains, and human breast cancer cells.


Asunto(s)
Técnicas Biosensibles , Grafito/química , Nanopartículas/química , Resinas Acrílicas/química , Neoplasias de la Mama/genética , Femenino , Oro/química , Humanos , Dióxido de Silicio/química , Espectrometría Raman
2.
Angew Chem Int Ed Engl ; 56(14): 3822-3826, 2017 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-28199758

RESUMEN

Reported is a new shell-based spectroscopic platform, named mechanical trap surface-enhanced Raman spectroscopy (MTSERS), for simultaneous capture, profiling, and 3D microscopic mapping of the intrinsic molecular signatures on the membrane of single live cells. By leveraging the functionalization of the inner surfaces of the MTs with plasmonic gold nanostars, and conformal contact of the cell membrane, MTSERS permits excellent signal enhancement, reliably detects molecular signatures, and allows non-perturbative, multiplex 3D surface imaging of analytes, such as lipids and proteins on the surface of single cells. The demonstrated ability underscores the potential of MTSERS to perform 3D spectroscopic microimaging and to furnish biologically interpretable, quantitative, and dynamic molecular maps in live cell populations.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Imagen Molecular , Análisis de la Célula Individual , Línea Celular Tumoral , Femenino , Humanos , Tamaño de la Partícula , Espectrometría Raman , Propiedades de Superficie
3.
Biomed Opt Express ; 14(12): 6114-6126, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38420330

RESUMEN

We used diffuse reflectance spectroscopy to quantify tissue absorption and scattering-based parameters in similarly sized tumors derived from a panel of four isogenic murine breast cancer cell lines (4T1, 4T07, 168FARN, 67NR) that are each capable of accomplishing different steps of the invasion-metastasis cascade. We found lower tissue scattering, increased hemoglobin concentration, and lower vascular oxygenation in indolent 67NR tumors incapable of metastasis compared with aggressive 4T1 tumors capable of metastasis. Supervised learning statistical approaches were able to accurately differentiate between tumor groups and classify tumors according to their ability to accomplish each step of the invasion-metastasis cascade. We investigated whether the inhibition of metastasis-promoting genes in the highly metastatic 4T1 tumors resulted in measurable optical changes that made these tumors similar to the indolent 67NR tumors. These results demonstrate the potential of diffuse reflectance spectroscopy to noninvasively evaluate tumor biology and discriminate between indolent and aggressive tumors.

4.
Cancer Res ; 79(8): 2054-2064, 2019 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-30819665

RESUMEN

Delay in the assessment of tumor response to radiotherapy continues to pose a major challenge to quality of life for patients with nonresponsive tumors. Here, we exploited label-free Raman spectroscopic mapping to elucidate radiation-induced biomolecular changes in tumors and uncovered latent microenvironmental differences between treatment-resistant and -sensitive tumors. We used isogenic radiation-resistant and -sensitive A549 human lung cancer cells and human head and neck squamous cell carcinoma (HNSCC) cell lines (UM-SCC-47 and UM-SCC-22B, respectively) to grow tumor xenografts in athymic nude mice and demonstrated the molecular specificity and quantitative nature of Raman spectroscopic tissue assessments. Raman spectra obtained from untreated and treated tumors were subjected to chemometric analysis using multivariate curve resolution-alternating least squares (MCR-ALS) and support vector machine (SVM) to quantify biomolecular differences in the tumor microenvironment. The Raman measurements revealed significant and reliable differences in lipid and collagen content postradiation in the tumor microenvironment, with consistently greater changes observed in the radiation-sensitive tumors. In addition to accurately evaluating tumor response to therapy, the combination of Raman spectral markers potentially offers a route to predicting response in untreated tumors prior to commencing treatment. Combined with its noninvasive nature, our findings provide a rationale for in vivo studies using Raman spectroscopy, with the ultimate goal of clinical translation for patient stratification and guiding adaptation of radiotherapy during the course of treatment. SIGNIFICANCE: These findings highlight the sensitivity of label-free Raman spectroscopy to changes induced by radiotherapy and indicate the potential to predict radiation resistance prior to commencing therapy.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias de Cabeza y Cuello/patología , Neoplasias Pulmonares/patología , Tolerancia a Radiación , Espectrometría Raman/métodos , Microambiente Tumoral/efectos de la radiación , Animales , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Ratones , Ratones Desnudos , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
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