Nanozyme-integrated microneedle patch for enhanced therapy of cutaneous squamous cell carcinoma by breaking the gap between H 2 O 2 self-supplying chemodynamic therapy and photothermal therapy.

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers with increasing incidence worldwide. However, it is still challenging to prevent the relapse of cSCC due to poor drug penetration across the stratum corneum. Herein, we report the design of a microneedle patch loaded with MnO 2 /Cu 2 O nanosheets and combretastatin A4 (MN-MnO 2 /Cu 2 O-CA4) for the enhanced therapy of cSCC. The prepared MN-MnO 2 /Cu 2 O-CA4 patch could effectively deliver adequate drugs locally into the tumor sites. Moreover, the glucose oxidase (GOx)-mimicking activity of MnO 2 /Cu 2 O could catalyze glucose to produce H 2 O 2 , which combined with the released Cu to induce a Fenton-like reaction to efficiently generate hydroxyl radicals for chemodynamic therapy. Meanwhile, the released CA4 could inhibit cancer cell migration and tumor growth by disrupting the tumor vasculature. Moreover, MnO 2 /Cu 2 O was endowed with the ability of photothermal conversion under the irradiation of near-infrared (NIR) laser, which could not only kill the cancer cells but also promote the efficiency of the Fenton-like reaction. Significantly, the photothermal effect did not compromise the GOx-like activity of MnO 2 /Cu 2 O, which guaranteed enough production of H 2 O 2 for the sufficient generation of hydroxyl radicals. This work may open avenues for constructing MN-based multimodal treatment for the efficient therapy of skin cancers.