MiRNAs in Interstitial Skin Fluid Sampled with Swellable Hydrogel Microneedles Are Locally Deregulated Near Malignant Skin Lesions in Early Stages of Cutaneous Squamous Cell Carcinoma

Interrogating molecular biomarkers in bodily fluids has emerged as a clinically useful strategy for the early diagnosis of many cancer types. Interstitial skin fluid is currently being explored as a possible alternative to blood, containing the same types of biomarkers but lacking cells and debris that hold little or no clinical value. The discovery and validation of molecular biomarkers with diagnostic or prognostic value and the development of clinical tests based on their detection require minimally invasive technologies capable of sampling this fluid in a pain-free manner. Biomarkers must also be easily recoverable for follow-on analysis. Herein, we combine standard genomic approaches with innovative bioengineering technologies to demonstrate that short noncoding miRNAs are significantly deregulated in extracellular skin fluid surrounding malignant skin lesions, providing a yet largely unexplored window of opportunity for early diagnosis of skin cancers. Hydrogel-based microneedle patches offering clinically useful sampling capacity were developed that enable the rapid capture and recovery of endogenous miRNAs from human skin through deformation of the epidermal-dermal junction. Using mouse models of cutaneous squamous cell carcinoma, a significantly greater level of deregulation of selected miRNAs was observed in perilesional skin fluid compared to that in blood levels.