Port wine stain (PWS) is a congenital and progressive malformations of the dermal capillaries. Pulsed dye laser (POL) irradiation in the visible wavelength range of 585-600 nm remains as the gold standard of treatment. The underlying treatment principle is based on the absorption of POL light by hemoglobin to induce irreversible photothermal coagulation of the vasculature. However, therapeutic efficacy with POLs remains limited due to insufficient penetration of light in skin, and non-specific absorption by the epidermal melanin pigments. Clinically acceptable outcomes are achieved in only about 20% of patients with diminishing returns beyond five treatment sessions. Our long-term objective is the development of a new therapeutic approach based on intravascular administration of optical micro-particles, fabricated from erythrocytes, as targets for pulsed near infrared (NIR) laser treatment at 755 nm. These micro-particles are doped with indocyanine green (ICG), the only FOA-approved NIR chromophore. The underlying premise is based on reduced absorption of light by melanin, strong ICG absorption, and availability of dermatological lasers at 755 nm. A particularly innovative feature of these micro-particles is that their membrane is enriched with cholesterol to prevent the flipping of phosphatidylserine from the inner to the outer leaflet of the membrane, which would otherwise serve as a signal for removal of the particles from the vasculature. We refer to these micro-particles as c⁺- µNETs. By using c⁺-µNETs, we aim to prolong the circulation time of ICG, and increase its availability in the lesion vasculature so that more sites can be treated during a given session, ultimately leading to minimal therapeutic sessions to clear the stain. Another innovative aspect is the use of transgenic mice whose melanin content can be varied in a controllable manner to simulate the epidermal response of PWS with different pigmentations to 755 nm laser irradia