Topical therapy is a favored route for treating skin cancers, but remain many challenges, such as low delivery efficiency, limited tumor tissue penetration, and unsatisfactory blood circulation. Here, a self-heating microneedle (MN) patch with multilevel structures, including a dissolvable base for rapid drug release, a degradable tip for sustained drug release, and a self-heating substrate is described. The thermally enhanced drug release performance is validated through both in vitro and in vivo experiments. High tumor therapeutic efficacy can be achieved due to the rapid release of 5-fluorouracil, while the sustained release of thymoquinone endows the MN patch with long-term tumor inhibition ability. It is further demonstrated the feasibility of such an MN patch for in vivo topical therapy of cutaneous squamous cell carcinoma with high efficacy, low side effects, and long-term inhibition of recurrence. This self-heating MN patch holds great promise for potential clinical applications, especially for the treatment of skin cancers.
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