Stimulated emission image of the microvascular network in a mouse's ear. The sample shows in red the blood vessel network surrounding green-colored sebaceous glands. Sebaceous glands are microscopic glands located in skin that secrete an oily and waxy matter used to lubricate the skin and hair of animals. A technique called confocal reflectance was simultaneously used to record the green-colored sebaceous glands. The image is based on contrasts of non-fluorescent hemoglobin molecules.

In the zoomed-in image, individual red blood cells are lined up within a single capillary approximately five micrometers in diameter. A micrometer is one-millionth of a meter.

The structure and hemoglobin-dynamics of blood vessels play a major role in many biomedical processes, such as angiogenesis in tumors and cerebral oxygen delivery in the brain. Angiogenesis is the growth of new blood vessels from pre-existing vessels. It is also a fundamental step in the transition of tumors from a dormant to malignant state.

Credit: Wei Min and Sijia Lu, Department of Chemistry and Chemical Biology, Harvard University

Stimulated emission image of the delivery of "toluidine blue O" to an area of freshly cut mouse ear skin at the depth of three micrometers. The image was taken 30 minutes after topical application of toluidine blue O. A micrometer is one-millionth of a meter. Toluidine blue O, or TBO, is a molecular dye with an affinity for cancer cells in living organisms. The non-fluorescent drug is used in cancer therapy to locate cancer cells, which are then killed by radiation.

The image was taken at the surface layer of stratum corneum, which is the outer most layer of skin. The image shows TBO accumulated in the protein phase of the polygonal cells rather than in the lipid-rich intercellular space.

Credit: Wei Min and Sijia Lu, Department of Chemistry and Chemical Biology, Harvard University

Stimulated emission image of the delivery of "toluidine blue O" to the same area of freshly cut mouse ear skin as in the second image. Image was taken at a depth of 25 micrometers 30 minutes after topical application of the molecular dye. A micrometer is one-millionth of a meter.

The image shows a rich distribution of toluidine blue O, or TBO, following the subcellular cytoplasm of basal keratinocytes. Basal keratinocytes are the major cellular constituents of skin and located in the deepest layer of skin.

The top and middle images support that the hydrophilic, or water loving, path is the main pathway for transdermal drug delivery of TBO. Subcellular localization of TBO is crucial because it influences both the level and the kinetics of inducing cellular death or apoptosis.

Credit: Wei Min and Sijia Lu, Department of Chemistry and Chemical Biology, Harvard University