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目的:构建负载化疗药物并具有光热和光动力联合治疗效果的介孔碳纳米粒(MCNs),研究其体外抗多药耐药肿瘤的作用。方法:利用低浓度水热法制备MCNs,通过混酸超声法将MCNs表面羧基化制成MCNs-COOH(MCNC),对其形貌、表面性质等进行表征。利用吸附法构建负载阿霉素(ADR)的ADR/MCNC,通过紫外吸光度计算其载药量,利用透析法考察其释放特性。选用耐ADR人乳腺癌MCF-7/ADR细胞通过共聚焦激光显微镜观察ADR/MCNC的细胞摄取和定位,MTT法考察ADR/MCNC的细胞毒性,用流式细胞术测定NIR光照下细胞内活性氧自由基(ROS)水平。结果:所制备的MCNC的粒径约为90 nm,表面含有羧基,BET比表面积为541.62 m2/g,孔容为0.34 cm3/g,孔径分布约为2.5 nm,具有显著光热效应。ADR/MCNC的载药量为47.4%,具有pH/NIR响应性释放特性;NIR光照下能促进ADR的细胞摄取和核内蓄积,能诱导MCF-7/ADR细胞产生ROS,并对细胞有显著的抑制作用。结论:成功制得MCNs,此外ADR/MCNC具有抗多药耐药肿瘤的作用。
OBJECTIVE: To establish the mesoporous carbon nano-drug delivery system (MCNs) with chemotherapy drugs loaded and holding photothermal and photodynamic combined effect, and study its anti-multidrug-resistant tumor effect in vitro. METHODS: MCNs was prepared by low-concentration hydrothermal route, and the MCNs surface was carboxylated by the mixed acid ultrasound method to made MCNs-COOH (MCNC). The morphology and surface properties were evaluated. Adriamycinc (ADR) was loaded into MCNC to fabricate ADR/MCNC via adsorption method. Drug loading capacity was calculated by UV, and drug release profile was investigated by dialysis method. ADR-resistant human breast cancer MCF-7/ADR cells were chosen, and cell uptake and positioning of ADR/MCNC were observed by confocal laser microscopy; cytotoxicity of ADR/MCNC was detected by MTT method; and intracellular reactive oxygen species (ROS) level under NIR irradiation was measured by flow cytometry. RESULTS: The particle size of prepared MCNs was about 90 nm, with carboxyl in surface. The specific surface area was 541.62 m2/g, pore volume was 0.34 cm3/g, and pore size distribution was 2.5 nm, with significant photothermal effect. The drug loading capacity of ADR/MCNC was 47.4%, showing pH/NIR responsiveness release characteristics. It can promote ADR in cell uptake and nuclear accumulation and induce MCF-7/ADR cell to generate ROS under NIR irradiation, with significant inhibitory effect. CONCLUSIONS: MCNs is prepared successfully, and ADR/MCNC has an effect on anti-multidrug-resistant tumors.
介孔碳纳米给药系统光热疗法光动力疗法响应性肿瘤多药耐药
Mesoporous carbonNano-drug delivery systemPhotothermal therapyPhotodynamic therapyResponsiveTumor multidrug resistance
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