Deepened Photodynamic Therapy through Skin Optical Clearing Technology in the Visible Light Window

The trade-off that shorter wavelength light facilitates the efficient generation of reactive oxygen species (ROS) from photosensitizer (PS) while facing the drawback of limited penetration depth through skin tissue restricts the further development of photodynamic therapy (PDT). Here, we address this contradiction and achieve visible-light-tailored deep PDT combined with the skin optical clearing technology. With the help of the prepared skin optical clearing gel, the refractive index inhomogeneity between skin tissue components is greatly attenuated, and the light scattering effect within the skin tissue is remarkably reduced. As a consequence, the transmittance of visible light at 600 nm through in vitro porcine skin and in vivo mouse skin after treatment increases from approximately 10 and 40 to 70 and 70%, respectively. Furthermore, in the tumor cell eradication experiment, the local ROS generation efficiency in the experimental group is several times higher than that in the control group owing to improved visible transmittance, which is thus responsible for the complete eradication of tumor cells, even when shaded by skin tissue. The results suggest that this strategy may serve as a valuable supplement to the current deep PDT strategies.