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Cuproptosis-Inducible Chemotherapeutic/Cascade Catalytic Reactor System for Combating with Breast Cancer
Authors:Song Yi Lee  Ji-Hye Seo  Sungyun Kim  ChaeRim Hwang  Da In Jeong  JiHye Park  Mingyu Yang  Ji Won Huh  Hyun-Jong Cho
Affiliation:1. Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, 24341 Republic of Korea

Kangwon Institute of Inclusive Technology, Kangwon National University, Chuncheon, Gangwon, 24341 Republic of Korea;2. Department of Pharmacy, College of Pharmacy, Kangwon National University, Chuncheon, Gangwon, 24341 Republic of Korea

Abstract:Cascade hydroxyl radical generating hydrogel reactor structures including a chemotherapeutic agent are invented for multiple treatment of breast cancer. Glucose oxidase (GOx) and cupric sulfate (Cu) are introduced for transforming accumulated glucose (in cancer cells) to hydroxyl radicals for starvation/chemodynamic therapy. Cu may also suppress cancer cell growth via cuproptosis-mediated cell death. Berberine hydrochloride (BER) is engaged as a chemotherapeutic agent in the hydrogel reactor for combining with starvation/chemodynamic/cuproptosis therapeutic modalities. Moreover, Cu is participated as a gel crosslinker by coordinating with catechol groups in hyaluronic acid-dopamine (HD) polymer. Controlling viscoelasticity of hydrogel reactor can extend the retention time following local injection and provide sustained drug release patterns. Low biodegradation rate of designed HD/BER/GOx/Cu hydrogel can reduce dosing frequency in local cancer therapy and avoid invasiveness-related inconveniences. Especially, it is anticipated that HD/BER/GOx/Cu hydrogel system can be applied for reducing size of breast cancer prior to surgery as well as tumor growth suppression in clinical application.
Keywords:chemodynamic therapy  chemotherapy  cuproptosis  Fenton-like reaction  hydrogel
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