Zinc oxide nanoparticles (ZnO NPs) are commonly used in sunscreens to reduce the risk of skin cancer by blocking
ultraviolet radiation. ZnO NPs absorption through the transdermal route may not cause high health risk as inhalation or
ingestion. However, in practical usage of sunscreens and cosmetics, ZnO NPs are topically applied to a large area of
skin with long periods hence the potential absorption amount of ZnO NPs is still need to be concerned. Therefore, if the
ZnO NPs are able the pass the barrier of normal skin, the pathways of transdermal delivery and the factors of
enhancements become important issues. In this work, multiphoton microscopy provides us a non-invasive visualization
of ZnO NPs in skin. Moreover, we quantitatively analyzed the enhancement of oleic acid and ethanol.
Due to the fact that photoluminance of ZnO NPs spectrally overlaps autofluorence from skin stratum corneum (SC) and
high turbidity of both ZnO NPs and SC, it is difficult to resolve the distribution of ZnO NPs in skin by using
fluorescence microscopy. In this work, the second harmonic generation (SHG) signals from ZnO NPs which double the
frequency of excitation source to characterize the delivery pathways and penetration depth in skin. Moreover, we
quantitatively compare the ZnO NPs delivery efficiency in normal skin and in skins with three chemically enhancing
conditions: ethanol, oleic acid and the combination of ethanol and oleic acid.