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Enzyme-Driven Release of Loads from Nucleic Acid-Capped Metal-Organic Framework Nanoparticles

机译:核酸驱动的金属-有机金属骨架纳米颗粒负载的酶驱动释放。

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摘要

Nucleic acid-modified UiO-68 metal-organic framework nanoparticles, NMOFs, are loaded with the anticancer drug camptothecin (or drug models), and the loaded NMOFs are capped with sequence-specific duplex units. The NMOFs are unlocked by the biocatalytic decomposition of the duplex capping units that result in the release of the drug (or drug models). The enzymes used are DNase I, a nicking enzyme (Nt.BbvCI), an endonuclease (EcoRI), and an exonuclease III (Exo III). Camptothecin-loaded NMOFs, capped by tailored hairpin nucleic acids being cooperatively unlocked by adenosine triphosphate (ATP), that is overexpressed in cancer cells, and Exo III are prepared. The camptothecin-loaded NMOFs reveal that selective cytotoxicity toward MDA-MB-231 cancer cells and approximate to 55% apoptosis of the cancer cells is observed after 5 days of treatment with the NMOFs, while only approximate to 15% apoptosis of epithelial MCF-10A breast cells is observed.
机译:核酸修饰的UiO-68金属-有机骨架纳米颗粒NMOF装有抗癌药物喜树碱(或药物模型),并且装载的NMOF装有序列特异性双链体单元。 NMOF通过双链帽单元的生物催化分解而解锁,从而导致药物(或药物模型)的释放。使用的酶是DNase I,切刻酶(Nt.BbvCI),核酸内切酶(EcoRI)和核酸外切酶III(Exo III)。制备了喜树碱负载的NMOF,其由特制的发夹核酸封端,并由癌细胞中过表达的三磷酸腺苷(ATP)共同解锁,并制备了Exo III。载有喜树碱的NMOFs显示,用NMOFs治疗5天后,观察到对MDA-MB-231癌细胞的选择性细胞毒性和约55%的癌细胞凋亡,而上皮MCF-10A的凋亡仅约15%观察到乳腺细胞。

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