NO-releasing nanomotor-loaded microneedles induce melanoma cell death via intracellular self-assembly.

Due to the particularity of melanoma location, traditional drug delivery methods face difficulties in penetrating skin tissue and specifically clearing melanoma cells. Here, we designed a hyaluronic acid microneedle drug delivery system loaded with nanomotors which can effectively penetrate the skin tissue and deliver the therapeutic components to melanoma and specifically remove melanoma cells. The loaded nanomotors were prepared by radical polymerization of methacryloyl modified L-arginine (MA) and L-tyrosine (MTyr), named as MA/MTyr nanomotor. The microneedle drug delivery system can use the rigid structure of microneedles to break through the skin barrier and deliver nanomotors to deep tissues. The MA endowed them with the ability to sensitively sense the highly expressed inducible nitric oxide synthase in the tumor microenvironment, so as to realize the effective targeting of melanoma in skin tissue and uptake by tumor cells. Subsequently, the MTyr can produce quinone-enriched intermediates that can induce cell death under the catalysis of tyrosinase that was specifically highly expressed in melanoma cells, and self-assembled to form micron scale fibers through intermolecular hydrogen bonding interactions, thereby inducing melanoma cells to swell. This process synergistically promoted melanoma cell death without occurring in normal cells. The experimental results of cell and animal models confirmed the good therapeutic effect of the nanomotor loaded microneedles, which provided a new therapeutic concept and strategy for the development of therapeutic methods specifically for melanoma.