金属有机骨架(MOFs)具有高孔隙率和比表面积大特点,可以用作药物递送载体靶向治疗肿瘤。首先,通过水热法在马弗炉内高温结晶合成金属有机骨架纳米颗粒(MIL-88B-NH2)。负载精氨酸(D-Arg)和葡萄糖氧化酶(GOX)形成D-Arg@MIL-88B-NH2/GOX纳米颗粒。采用透射电镜(TEM)、扫描电镜(SEM)、Zeta电位、红外光谱(FT-IR)和电感耦合等离子体发射光谱(ICP-AES)等手段对纳米颗粒进行表征。结果表明:所制备的纳米材料粒径均一(约为190nm),具有较为立体的梭形结构,同时通过表征证实了载药纳米颗粒的成功制备。体外细胞实验表明纳米颗粒可以靶向癌细胞、提高抗肿瘤效果和促进细胞凋亡。
Metal-organic frameworks (MOFs) can be used as a drug delivery carrier for targeted treatment of tumors due to their high porosity and large specific surface area.First,metal-organic framework nanoparticles (MIL-88B-NH2) was synthesized by hydrothermal crystallization in a muffle furnace at high temperature.Then,D-Arg@MIL-88B-NH2/GOX nanoparticles were formed by loading Arginine (D-Arg) and Glucose Oxidase (GOX).The nanoparticles were characterized by TEM,SEM,FT-IR,Zeta potentials and ICP-AES.The results showed that the prepared nanomaterials had a uniform particle size (about 190nm) and a relatively three-dimensional shuttle structure.At the same time,the successful preparation of drug-loaded nanoparticles was confirmed by characterization.In vitro cell experiments indicated that nanoparticles could target cancer cells,improve anti-tumor effect and promote cell apoptosis.
[1] Fu L,Zhang W,Zhou X,et al.Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma[J].Bioactive Materials,2022,17(43):221-33.
[2] Xia Q,Wang H,Huang B,et al.State-of-the-art advances and challenges of iron-based metal organic frameworks from attractive features,synthesis to multifunctional applications[J].Small,2019,15(2):1803088.
[3] Ma L,Jiang F,Fan X,et al.Metal-organic-framework-engineered enzyme-mimetic catalysts[J].Advanced Materials,2020,32(49):2003065.
[4] Wan X,Song L,Pan W,et al.Tumor-targeted cascade nanoreactor based on metal-organic frameworks for synergistic ferroptosis-starvation anticancer therapy[J].ACS Nano,2020,14(9):11017-28.
[5] Wu Q,Du Q,Sun X,et al.MnMOF-based microwave-glutathione dual-responsive nano-missile for enhanced microwave thermo-dynamic chemotherapy of drug-resistant tumors[J].Chemical Engineering Journal,2022,439(3):135582.
[6] Liu Z,Li T,Han F,et al.A cascade-reaction enabled synergistic cancer starvation/ROS-mediated/chemo-therapy with an enzyme modified Fe-based MOF[J].Biomaterials Science,2019,7(9):3683-3692.
[7] Xiang X,Pang H,Ma T,et al.Ultrasound targeted microbubble destruction combined with Fe-MOF based bio-/enzyme-mimics nanoparticles for treating of cancer[J].Journal of Nanobiotechnology,2021,19(1):1-14.
[8] Ding Y,Wan J,Zhang Z,et al.Localized Fe(Ⅱ)-induced cytotoxic reactive oxygen species generating nanosystem for enhanced anticancer therapy[J].ACS Applied Materials & Interfaces,2018,10(5):4439-4449.
[9] Xue T,Xu C,Wang Y,et al.Doxorubicin-loaded nanoscale metal-organic framework for tumor-targeting combined chemotherapy and chemodynamic therapy[J].Biomaterials Science,2019,7(11):4615-23.
[10] Ma Y,Zhao Y,Bejjanaki N K,et al.Nanoclustered cascaded enzymes for targeted tumor starvation and deoxygenation-activated chemotherapy without systemic toxicity[J].ACS Nano,2019,13(8):8890-902.
[11] Mei L,Ma D,Gao Q,et al.Glucose-responsive cascaded nanocatalytic reactor with self-modulation of the tumor microenvironment for enhanced chemo-catalytic therapy[J].Materials Horizons,2020,7(7):1834-1844.
[12] Zhu Y,Shi H,Li T,et al.A dual functional nanoreactor for synergistic starvation and photodynamic therapy[J].ACS Applied Materials & Interfaces,2020,12(16):18309-18318.
[13] Zhang L,Wang Z,Zhang Y,et al.Erythrocyte membrane cloaked metal-organic framework nanoparticle as biomimetic nanoreactor for starvation-activated colon cancer therapy[J].ACS Nano,2018,12(10):10201-10211.
[14] Wei C,Liu Y,Zhu X,et al.Iridium/ruthenium nanozyme reactors with cascade catalytic ability for synergistic oxidation therapy and starvation therapy in the treatment of breast cancer[J].Biomaterials,2020,238(7):119848.
[15] Gao G,Jiang Y W,Guo Y,et al.Enzyme-mediated tumor starvation and phototherapy enhance mild-temperature photothermal therapy[J].Advanced Functional Materials,2020,30(16):1909391.
[16] Tejero J,Shive S,Gladwin M T.Sources of vascular nitric oxide and reactive oxygen species and their regulation[J].Physiological Reviews,2019,99(1):311-379.
[17] Deng Y,Jia F,Chen X,et al.ATP suppression by pH-activated mitochondria-targeted delivery of nitric oxide nanoplatform for drug resistance reversal and metastasis inhibition[J].Small,2020,16(23):2001747.
[18] Wang Z,Zhan M,Li W,et al.Photoacoustic cavitation-ignited reactive oxygen species to amplify peroxynitrite burst by photosensitization-free polymeric nanocapsules[J].Angewandte Chemie International Edition,2021,60(9):4720-4731.
[19] Liu R,Peng Y,Lu L,et al.Near-infrared light-triggered nano-prodrug for cancer gas therapy[J].Journal of Nanobiotechnology,2021,19(1):1-23.
[20] Nagase S,Takemura K,Ueda A,et al.A novel nonenzymatic pathway for the generation of nitric oxide by the reaction of hydrogen peroxide and D-or L-arginine[J].Biochemical and Biophysical Research Communications,1997,233(1):150-153.
[21] Wang X Q,Gao F,Zhang X Z.Initiator-loaded gold nanocages as a light-induced free-radical generator for cancer therapy[J].Angewandte Chemie,2017,129(31):9157-9161.
基金资助
上海市科学技术委员会资助(20DZ2254900、21WZ2501300和20DZ2254900);生物医药纺织材料“111工程”中国教育部(B07024)
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