多功能铜基纳米酶的制备及体外抗肿瘤活性OA

To address the constrains imposed by insufficient hydrogen peroxide(H2O2)and high glutathione(GSH)expression in tumor cells on the efficacy of chemodynamic therapy(CDT),zeolitic imidazolate framework-8(ZIF-8)loaded with disulfiram(DSF)and 3-amino-1,2,4-triazole(3-AT)was synthesized via a one-pot approach.Subsequently,hyaluronic acid(HA)-modified cupric peroxide(CuO2)was in-situ grown on its surface through biomineralization to construct a multifunctional copper-based nanozyme ADZCH(3-AT/DSF@ZIF-8@CuO2-HA).This nanoplatform disrupts the intratumoral H2O2 homeostasis,depletes GSH,and synchronously delivers DSF and Cu2+via cascade catalysis,thereby enhancing CDT and sensitizing tumors to DSF-based chemotherapy.The results of physicochemical characterization indicated that ADZCH presented a uniform core-shell structure with favorable dispersibility.Its particle size and Zeta potential were 196.5 nm and-19.5 mV,respectively.It possessed a microporous structure with a specific surface area of 81.860 0 m2/g,and demonstrated efficient loading capacity for DSF and 3-AT,achieving drug loading efficiencies of 5.91%and 45.07%,respectively.Moreover,ADZCH can continuously and slowly release drugs in an acidic environment and maintain good stability under diverse physiological conditions.In vitro functional assays verified that ADZCH catalytically generated H2O2 and hydroxyl radicals while concurrently depleting GSH in a concentration-and incubation time-dependent manner.Cellular uptake experiments showed that HA modification significantly improved the uptake of nanoparticles by 4T1 cells.Cytotoxicity tests showed that 80 μg/mL ADZCH had a significant cytotoxic effect on 4T1 cells but no significant toxicity on L929 cells.DCFH-DA probe detection indicated that ADZCH could significantly induce intracellular reactive oxygen species(ROS)generation,thereby enhancing CDT efficacy.Live/dead staining experiments showed that ADZCH efficiently induced apoptosis,with the proportion of dead cells reaching 94.74%,demonstrating its promising potential for anti-tumor applications.This study provides new research ideas and experimental basis for overcoming the tumor microenvironment barrier and enhancing the anti-tumor effect of CDT combined with chemotherapy.