Cascade-catalysed nanocarrier degradation for regulating metabolism homeostasis and enhancing drug penetration on breast cancer

Cascade-catalysed nanocarrier degradation for regulating metabolism homeostasis and enhancing drug penetration on breast cancer

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Abstract The abnormal structure of tumor vascular seriously hinders the delivery and deep 9 Piece Dining Room penetration of drug in tumor therapy.Herein, an integrated and tumor microenvironment (TME)-responsive nanocarrier is designed, which can dilate vessle and improve the drug penetration by in situ releasing nitric oxide (NO).Briefly, S-nitroso-glutathione (GSNO) and curcumin (Cur) were encapsulatd into the Cu-doped zeolite imidazole framework-8 (Cu-ZIF-8) and modified with hyaluronic acid.The nanocarrier degradation in the weakly acidic of TME releases Cu2+, then deplete overexpressed intratumourally glutathione and transformed into Cu+, thus disrupting the balance between nicotinamide adenine dinucleotide phosphate and flavin adenine dinucleotide (NADPH/FAD) during the metabolism homeostasis of tumor.

The Cu+ can generate highly toxic hydroxyl radical through the Fenton-like reaction, enhancing the chemodynamic therapeutic effect.In addition, Cu+ also decomposes GSNO to release NO by ionic reduction, leading to vasodilation and subscribfy_subscription_product increased vascular permeability, significantly promoting the deep penetration of Cur in tumor.Afterwards, the orderly operation of cell cycle is disrupted and arrested in the S-phase to induce tumor cell apoptosis.Deep-hypothermia potentiated 2D/3D fluorescence imaging demonstrated nanocarrier regulated endogenous metabolism homeostasis of tumor.

The cascade-catalysed multifunctional nanocarrier provides an approach to treat orthotopic tumor.