Nonlinear optical microscopy for drug delivery monitoring and cancer tissue imaging

Abstract

A multimodal nonlinear optical microscope that combines coherent anti-Stokes Raman scattering (CARS), two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG) and sum-frequency generation (SFG) was developed and applied to image breast cancer tissue and MCF-7 cells as well as monitoring anticancer drug delivery in live cells. TPEF imaging showed that drugs are preferentially localized in the cytoplasm and the nuclear envelope in resistant cells. Moreover, the extracellular matrix was observed by TPEF signals arising from elastin's autofluorescence and SHG signals from collagen fibrils in breast tissue sections. Additionally, CARS signals arising from proteins and (PO 2 ) − allowed identification of tumors. Label-free imaging with chemical contrast of significant components of cancer cells and tissue suggests the potential of multimodal nonlinear optical microscopy for early detection and diagnosis of cancer.

Label-free identification and characterization of living human primary and secondary tumour cells

“…34 Stacks of 10 images were acquired at 1 µm separation, and converted into a 2-dimensional image by Z-projection at maximum intensity to observe all the lipid droplets throughout the cell. The resolution of the system was previously measured as 250 nm FWHM laterally and 1.1 µm FWHM axially.…”

“…30 It has been applied to cancer tissue to characterize regions, such as Basal Cell Carcinoma in skin, 11,30 and malignant from normal lung tissue. 34,35 CARS has also been used to investigate metastatic cellsmeasuring uptake of lipids, 36 and observing them in the bloodstream due to their higher lipid content. CARS has been used to identify regions as cancerousoffering label-free versions of Haematoxylin and Eosin stains with excellent correlation.…”

Recent advances in linear and nonlinear Raman spectroscopy. Part V

“…A multimodal nonlinear optical microscope that combines CARS, two‐photon excitation fluorescence, second‐harmonic generation and sum‐frequency generation was developed by Mouras et al . and applied to imaging breast cancer tissue and MCF‐7 cells as well as monitoring anticancer drug delivery in live cells . Label‐free imaging with chemical contrast of significant components of cancer cells and tissue suggests the potential of multimodal nonlinear optical microscopy for early detection and diagnosis of cancer.…”

Optical Spectroscopy of Biological Cells

“…23) [160]. Other useful vibrational bands include the broad -OH stretch mode near 3000 cm −1 (water) [161], the phosphate vibration at 1095 cm −1 (DNA/RNA) [141,162], and the -C=O stretch of the amide I band at 1600-1700 cm −1 (protein) [157]. CARS can be used to extract various chemical properties of tissue, such as the oxygenation state of blood [163].…”