Nonlinear opticalmicroscopy for drug delivery monitoring and cancer tissue imaging

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 (PO₂)^- 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.