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      Flying‐Saucer‐Shaped Nanoheterojunctions with Enhanced Colorectal Tumor Accumulation for Increased Oxidative Stress and Immunometabolic Regulation

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          Abstract

          The treatment outcomes of nanomedicines against colorectal cancer are severely restricted by their insufficient accumulation in the tumor tissues, unsatisfactory antitumor effect, and weak immunometabolic modulation. To address these issues, flying‐saucer‐shaped nanoheterojunctions by coating copper oxide (Cu xO) onto the surface of PEGylated zinc oxide (ZnO) nanoparticles are constructed. When exposed to ultrasound, the resultant Cu xO@ZnO nanoheterojunctions exhibit increased locomotor activities, facilitating colorectal mucus infiltration, deep tumor penetration, and tumor cell internalization. The decoration of Cu xO suppresses the rapid recombination of electrons and holes in Cu xO@ZnO exposed to ultrasound, promoting the production of singlet oxygen and hydroxyl radical, which are generated by Cu xO through a Fenton‐like chemodynamic reaction and Cu xO@ZnO through sonodynamic reaction. After rectal administration, the sono‐chemodynamic Cu xO@ZnO plus PD‐L1 antibodies effectively inhibit the growth of orthotopic and distant tumors. It elicits immunometabolic responses by inducing immunogenic cell death, activating the interferon genes signaling pathway stimulator, and inhibiting glucose transport and the glycolytic signaling pathways. This combined modality also increases the proportion of beneficial microbes ( e.g., Bifidobacterium) and decreases the abundance of harmful microorganisms ( e.g., Romboutsia) in the intestine. This treatment modality (Cu xO@ZnO plus ultrasound and PD‐L1 antibodies) is a promising strategy for the synergistic treatment of colorectal cancer.

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                Author and article information

                Contributors
                Journal
                Advanced Functional Materials
                Adv Funct Materials
                Wiley
                1616-301X
                1616-3028
                July 02 2024
                Affiliations
                [1 ] Department of Urology Urologic Surgery Center Xinqiao Hospital Third Military Medical University (Army Medical University) Chongqing 400037 China
                [2 ] College of Sericulture Textile and Biomass Sciences Southwest University Chongqing 400715 China
                [3 ] Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of Sciences Beijing 101400 China
                [4 ] 3Bs Research Group I3Bs — Research Institute on Biomaterials Biodegradables and Biomimetics University of Minho Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine AvePark Barco Guimarães 4805‐017 Portugal
                [5 ] ICVS/3B's‐PT Government Associate Laboratory Guimarães Braga 4800‐058 Portugal
                [6 ] Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Provincial People's Hospital School of Medicine University of Electronic Science and Technology of China Chengdu 610054 China
                Article
                10.1002/adfm.202402164
                f63b5bef-2a8a-49f3-98d8-728aa53ea4e1
                © 2024

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