Removable Photocatalysis Microneedle Reactor for Carbon Monoxide Delivery to Enhance Chemosensitization.

Carbon monoxide (CO) has emerged as a promising therapeutic agent, yet ensuring safe and precise CO delivery remains challenging. Here, we report a removable hydrogel-forming microneedle (MN) reactor for CO delivery via photocatalysis, with an emphasis on chemosensitization. Upon application, body fluids absorbed by the MNs dissolve the effervescent agents, leading to the generation of carbon dioxide (CO2) and triggering the release of the chemotherapeutics cisplatin. Meanwhile, the photocatalysts (PCs) trapped within MNs convert CO2 to CO under 660 nm light irradiation. These PCs can be removed by hydrogel-forming MNs, thereby mitigating potential biological risks associated with residual PCs. Both in vitro and in vivo experiments showed that MN-mediated CO delivery significantly improved tumor sensitivity to cisplatin by suppressing DNA repair, using an A375/CDDP melanoma model. This removable photocatalysis MN reactor offers safe and precise local delivery of CO, potentially creating new opportunities for CO or its combination therapies.

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.

Enhanced Transcutaneous Chemodynamic Therapy for Melanoma Treatment through Cascaded Fenton-like Reactions and Nitric Oxide Delivery.

Chemodynamic therapy (CDT) has emerged as a promising strategy for cancer treatment. However, its effectiveness has been hindered by insufficient hydrogen peroxide (H2O2) and high reductive glutathione (GSH) within tumors, which are the two main reasons for the inefficiency of Fenton/Fenton-like reaction-based CDT. Herein, we present a H2O2 boost-GSH depletion strategy for enhanced CDT to fight against melanoma through a microneedle (MN)-based transcutaneous delivery method. The MN system is composed of dissolvable polyvinylpyrrolidone integrated with stimuli-responsive prodrugs. Under an intracellular acidic environment, the smart release of H2O2 boosting components is triggered, subsequently initiating nitric oxide (NO) release and enhancing the Fenton-like reaction in a cascade manner. The generation of hydroxyl radicals (•OH), along with the depletion of GSH by NO, amplifies the oxidative stress within tumor cells, promoting apoptosis and ferroptosis. The antitumor efficacy of the MN patch is validated in an A375 mouse melanoma model. This "H2O2 boost-GSH depletion-Fenton killing" strategy expands the options for superficial tumor treatment through MN-mediated enhanced CDT.