On-Demand Release of Fucoidan from a Multilayered Nanofiber Patch for the Killing of Oral Squamous Cancer Cells and Promotion of Epithelial Regeneration.

Oral squamous cell carcinoma represents 90% of all oral cancers. Recurrence prevention remains an important prognostic factor in patients with oral squamous cell carcinoma, and the recovery of the oral epithelium post-surgery is still a challenge. Thus, there is an urgent need to develop a smart carrier material to realize the spatiotemporally controlled release of anticancer drugs, instead of multiple oral administrations, for recurrence prevention and promoting the reconstruction of injured epithelial tissues. Here, we developed a multi-layered nanofiber patch capable of the photothermal-triggered release of low-molecular-weight fucoidan (LMWF) from the sandwiched layer, together with electrospun fibers as the backing and top layers. The sandwiched layer was made of phase-change materials loaded with indocyanine green, a photosensitive dye, for the localized release of LMWF in response to near-infrared irradiation. We showed that the on-demand release of LMWF was able to kill oral cancer cells effectively. Furthermore, adding acellular dermal matrix to the top nanofiber layer improved the proliferation of human oral keratinocytes, while the hydrophobic back layer served as a barrier to prevent loss of the drug. Taken together, this study provides a feasible and smart material system for killing oral squamous cancer cells together with the recovery of oral epithelium.