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Cutting off the glucose supply by glucose oxidase (GOx) has been regarded as an emerging strategy in cancer starvation therapy. However, the standalone GOx delivery suffered suboptimal potency for tumor elimination and potential risks of damaging vasculatures and normal organs during transportation. To enhance therapeutic efficacy and tumor specificity, a site-specific activated dual-catalytic nanoreactor was herein constructed by embedding GOx and ferrocene in hyaluronic acid (HA)-enveloped dendritic mesoporous silica nanoparticles to promote intratumoral oxidative stress in cancer starvation. In this nanoreactor, the encapsulated GOx served as the primary catalyst that accelerated oxidation of glucose and generation of H 2 O 2 , while the covalently linked ferrocene worked as the secondary catalyst for converting the upstream H 2 O 2 to more toxic hydroxyl radicals ( • OH) via a classic Fenton reaction. The outmost HA shell not only offered a shielding layer for preventing blood glucose from oxidation during nanoreactor transportation, thus minimizing the probable oxidative damage to normal tissues, but also imparted the nanoreactor with targeting ability for facilitating its internalization into CD44-overexpressing tumor cells. After the nanoreactor was endocytosed by target cells, the HA shell underwent hyaluronidase-triggered degradation in lysosomes and switched on the cascade catalytic reaction mediated by GOx and ferrocene. The resulting glucose exhaustion and • OH accumulation would effectively kill cancer cells and suppress tumor growth via combination of starvation and oxidative stress enhancement. Both in vitro and in vivo results indicated the significantly amplified therapeutic effects of this synergistic therapeutic strategy based on the dual-catalytic nanoreactor. Our study provides a new avenue for engineering therapeutic nanoreactors that take effect in a tumor-specific and orchestrated fashion for cancer starvation therapy.

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Abnormal tumor microenvironment (TME) facilitates tumor proliferation and metastasis and establishes physiological barriers for effective transport of therapeutics inside the tumor,posing great challenges for cancer treatment. We designed ac ore-satellite sizet ransformable nanoframework (denoted as T-PFRT) that can synchronously adapt to and remold TME for augmenting photodynamic therapyt o inhibit tumor growth and prevent tumor metastasis.U pon matrix metalloproteinase 2(MMP2)-responsive dissociation of the nanoframework in TME, the core structure loaded with TGFb signaling pathway inhibitor and oxygen-carrying hemoglobin aims to stroma remodeling and hypoxia relief, allowing photosensitizer-encapsulated satellite particles to penetrate to deep-seated tumor for oxygen-fueled photodynamic therapy. T-PFRTc ould overcome the stroma and hypoxia barriers for delivering therapeutics and gain excellent therapeutic outcomes in the treatment of primary and metastatic tumors.

Underwater machinery withstands great resistance in the water, which can result in consumption of a large amount of power. inspired by the character that loach could move quickly in mud, the drag reduction mechanism of Paramisgurnus dabryanus loach is discussed in this paper. Subjected to the compression and scraping of water and sediments, a loach could not only secrete a lubricating mucus film, but also importantly, retain its mucus well from losing rapidly through its surface micro structure. In addition, it has been found that flexible deformations can maximize the drag reduction rate. this self-adaptation characteristic can keep the drag reduction rate always at high level in wider range of speeds. therefore, even though the part of surface of underwater machinery cannot secrete mucus, it should be designed by imitating the bionic micro-morphology to absorb and store fluid, and eventually form a self-lubrication film to reduce the resistance. In the present study, the Paramisgurnus dabryanus loach is taken as the bionic prototype to learn how to avoid or slow down the mucus loss through its body surface. This combination of the flexible and micro morphology method provides a potential reference for drag reduction of underwater machinery.