Fungal infections in skin are extremely stubborn and seriously threaten human health. In the process of antifungal treatment, it is a huge challenge that the stratum corneum of the skin and fungal biofilms form the drug transport barrier. Herein, a near-infrared (NIR) laser-propelled parachute-like nanomotor loaded with miconazole nitrate (PNM-MN) is fabricated to enhance transdermal drug delivery for synergistic antifungal therapy. Due to asymmetrically spatial distribution, PNM can generate a thermal gradient under NIR laser irradiation, thereby forming effective self-thermophoretic propulsion. The self-propulsion and photothermal effect of PNM play a major role in promoting fungal uptake and biofilm adhesion. Moreover, under laser irradiation, PNM-MN can obliterate plankton Candida albicans and mature biofilms by combining pharmacological therapy and photothermal therapy. More importantly, the drug effectively penetrated the skin to reach the infected site using the nanomotor with NIR laser irradiation. Moreover, PNM-MN with a NIR laser can eradicate fungal infections caused by C. albicans and facilitate the abscess ablation, showing a therapeutic effect in vivo better than that of PNM with a NIR laser or free MN groups, with negligible histological toxicity. Taken together, NIR laser-propelled PNM-MN, as an antifungal nanoagent, provides a promising strategy for transdermal delivery and antifungal therapy.

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Cell membrane‐cloaked nanoparticles are exploited as a promising drug carrier to enhance circulation, accumulation, penetration into tumor sites and cellular internalization. However, the effect of physicochemical properties (e.g., size, surface charge, shape, and elasticity) of cell membrane‐cloaked nanoparticles on nano‐bio interaction is rarely studied. In the present study, keeping the other parameters constant, erythrocyte membrane (EM)‐cloaked nanoparticles (nanoEMs) with different Young's moduli are fabricated by altering different kinds of nano‐core (i.e., aqueous phase core, gelatin nanoparticles, and platinum nanoparticles). The designed nanoEMs are used to investigate the effect of nanoparticle elasticity on nano‐bio interaction including cellular internalization, tumor penetration, biodistribution, blood circulation, and so on. The results demonstrate that the nanoEMs with intermediate elasticity (≈95 MPa) have a relatively higher increase in cellular internalization and inhibition of tumor cells migration than the soft (≈11 MPa) and stiff (≈173 MPa) ones. Furthermore, in vivo studies show that nanoEMs with intermediate elasticity preferentially accumulate and penetrate into tumor sites than the soft and stiff ones, while in circulation, softer nanoEMs show a longer blood circulation time. This work provides an insight for optimizing the design of biomimetic carriers and may further contribute to the selection of nanomaterials on biomedical application.

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Biocatalytic systems based on enzyme cascade reactions have attracted growing interest in the field of biocatalytic medicine. However, it is a major challenge to reasonably construct enzyme cascade reactions with high stability, selectivity, and catalytic efficiency for the in vivo biocatalytic application. Herein, two‐in‐one engineered glucose oxidase (GOx‐Fe0) is fabricated by a biomineralization strategy, through which a nanozyme (Fe0NP) is anchored within the inner cavity of GOx. Then, GOx‐Fe0 is immobilized in a pH‐sensitive metal–organic framework (MOF) zeolitic imidazolate framework‐8 (ZIF‐8) to establish a stable and effective MOF‐immobilized two‐in‐one engineered enzyme, GOx‐Fe0@ZIF‐8. In vitro studies show that GOx‐Fe0@ZIF‐8 exhibits excellent stability and high pH/glucose selectivity, and the shorter spacing between cascade enzymes can increase the cascade throughput and effectively improve the reaction efficiency of the enzyme cascade. In vivo experiments exhibit that GOx‐Fe0@ZIF‐8 solves the instability and systemic toxicity of free enzymes, and achieves deep tumor penetration and significant chemodynamic therapeutic efficacy through a pH/glucose‐selective enzyme cascade reaction in tumor site. Taken together, such an orchestrated enzyme engineering strategy can effectively improve enzyme stability, selectivity, and enzyme cascade reaction efficiency via chemical transformations, and also provide a promising strategy for the application of biocatalytic cascade reactions in vivo.