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Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein-alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα-cleavable peptide substrate linked by a self-immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45-fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle-assisted topical application enables sensitive detection of keloid cells in metabolically-active human skin tissue with a theoretical limit of detection down to 20 000 cells.

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This work reports a frozen spray-coating method for the fabrication of double-layered microneedles (MNs). Taking swellable methacrylated hyaluronic acid (MeHA)-derived MNs as the model, both hydrophobic molecules (Nile red, Cy5) and hydrophilic ones (FITC, FITC-Dextran, Insulin) can be homogeneously coated without impacting the mechanical properties of the original MeHA MNs. The prepared double-layered MNs can execute multiple roles. It is demonstrated that insulin-coated MeHA double-layered MNs allow the effective delivery of the insulin into circulation of mice for controlling the blood glucose level while they also permit the extraction of skin interstitial fluid for the timely analysis of the biomarker (glucose).

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