A photocatalytic carbon monoxide-generating effervescent microneedle patch for improved transdermal chemotherapy

Carbon monoxide (CO) is regarded as a promising therapeutic agent for chemotherapy sensitization. To simultaneously achieve controllable in situ CO production and efficient chemotherapeutics delivery is of great significance. Here, we presented a polyvinylpyrrolidone (PVP) core-shell microneedle (MN) system that encapsulated the effervescent component, photocatalyst, and doxorubicin hydrochloride (Dox·HCl) for CO-sensitized chemotherapy. Upon the insertion of MNs, the effervescent component, composed of sodium bicarbonate and tartaric acid, was exposed to interstitial fluid, leading to the burst release of carbon dioxide (CO2). The generated gas not only enhanced the diffusion of Dox·HCl but also served as a substrate for the photocatalytic generation of CO. From the experimental results, the photocatalyst CuS atomic layers (CAL) displayed an effective CO2 photoreduction performance, which could realize an irradiation time/intensity-dependent CO-controlled release. Ex vivo permeation studies demonstrated that effervescent CO2 production markedly enhanced the intradermal diffusion of Dox·HCl. Eventually, the robust antitumor efficacy of this versatile MN platform was proved in B16F10-bearing nude mice. This CO-sensitized chemotherapeutic MN system offered a novel strategy for transdermal gas/drug delivery, which might provide a new direction in tumor suppression.