In vivo quantification of quantum dot systemic transport in C57BL/6 hairless mice following skin application post-ultraviolet radiation

Samreen Jatana,Sarah J Phelan,Brian C Palmer,Robert Gelein,Lisa A Delouise

doi:10.1186/s12989-017-0191-7

Samreen Jatana, Sarah J Phelan + Show 3 more

Open Access

https://doi.org/10.1186/s12989-017-0191-7

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Abstract

BackgroundPrevious work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin. The goal of this work was to characterize the tissue distribution and mechanism of transport of nanoparticles beyond skin, with and without Ultraviolet Radiation (UVR) induced skin barrier disruption. Atomic absorption spectroscopy (AAS), flow cytometry and confocal microscopy were used to examine the effect of UVR dose (180 and 360 mJ/cm2 UVB) on the skin penetration and systemic distribution of quantum dot (QD) nanoparticles topically applied at different time-points post UVR using a hairless C57BL/6 mouse model.ResultsResults indicate that QDs can penetrate mouse skin, regardless of UVR exposure, as evidenced by the increased cadmium in the local lymph nodes of all QD treated mice. The average % recovery for all treatment groups was 69.68% with ~66.84% of the applied dose recovered from the skin (both epicutaneous and intracutaneous). An average of 0.024% of the applied dose was recovered from the lymph nodes across various treatment groups. When QDs are applied 4 days post UV irradiation, at the peak of the skin barrier defect and LC migration to the local lymph node, there is an increased cellular presence of QD in the lymph node; however, AAS analysis of local lymph nodes display no difference in cadmium levels due to UVR treatment.ConclusionsOur data suggests that Langerhans cells (LCs) can engulf QDs in skin, but transport to the lymph node may occur by both cellular (dendritic and macrophage) and non-cellular mechanisms. It is interesting that these specific nanoparticles were retained in skin similarly regardless of UVR barrier disruption, but the observed skin immune cell interaction with nanoparticles suggest a potential for immunomodulation, which we are currently examining in a murine model of skin allergy.

Highlights

Previous work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin
Cadmium (Cd) tissue distribution analysis by atomic absorption spectroscopy (AAS) Studies were performed to investigate whether the Ultraviolet Radiation (UVR) induced inside-out barrier defect as measured by Transepidermal Water Loss (TEWL), correlates with the outside-in penetration of quantum dot (QD)
We treated mice with QDs for 24 h topically applied either on day 0, 4 or 7 post-UVR irradiation (180 mJ/cm2 Ultraviolet Radiation B (UVB) light); day 4 being the peak of barrier defect post UV irradiation

Summary

Introduction

Previous work has demonstrated size, surface charge and skin barrier dependent penetration of nanoparticles into the viable layers of mouse skin. UVR exposure induces keratinocyte hyper-proliferation that leads to a thickened epidermis, a malformed stratum corneum and defective skin barrier that peaks 3 to 4 days post UVR as measured by transepidermal water loss (TEWL) [19]. Both UVA and UVB skin exposure have been directly linked to sunburn, photoaging, and carcinogenesis, the consequence of frequent use of nano-enabled products on UVR induced barrier defective skin is not well characterized [20, 21]. If NPs penetrate through the stratum corneum into the viable epidermis they have the potential to be transported to distal organs either by cellular uptake or through the lymphatic circulation and blood stream [19, 22]

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