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首页> 外文期刊>Advanced Functional Materials >Stimuli-Responsive Nucleic Acid-Based Polyacrylamide Hydrogel-Coated Metal-Organic Framework Nanoparticles for Controlled Drug Release
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Stimuli-Responsive Nucleic Acid-Based Polyacrylamide Hydrogel-Coated Metal-Organic Framework Nanoparticles for Controlled Drug Release

机译：刺激响应的基于核酸的聚丙烯酰胺水凝胶包衣的金属有机骨架纳米粒子用于药物的控制释放。

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摘要

The synthesis of doxorubicin-loaded metal-organic framework nanoparticles (NMOFs) coated with a stimuli-responsive nucleic acid-based polyacrylamide hydrogel is described. The formation of the hydrogel is stimulated by the crosslinking of two polyacrylamide chains, P-A and P-B, that are functionalized with two nucleic acid hairpins (4) and (5) using the strand-induced hybridization chain reaction. The resulting duplex-bridged polyacrylamide hydrogel includes the anti-ATP (adenosine triphosphate) aptamer sequence in a caged configuration. The drug encapsulated in the NMOFs is locked by the hydrogel coating. In the presence of ATP that is overexpressed in cancer cells, the hydrogel coating is degraded via the formation of the ATP-aptamer complex, resulting in the release of doxorubicin drug. In addition to the introduction of a general means to synthesize drug-loaded stimuli-responsive nucleic acid-based polyacrylamide hydrogel-coated NMOFs hybrids, the functionalized NMOFs resolve significant limitations associated with the recently reported nucleic acid-gated drug-loaded NMOFs. The study reveals substantially higher loading of the drug in the hydrogel-coated NMOFs as compared to the nucleic acid-gated NMOFs and overcomes the nonspecific leakage of the drug observed with the nucleic-acid-protected NMOFs. The doxorubicin-loaded, ATP-responsive, hydrogel-coated NMOFs reveal selective and effective cytotoxicity toward MDA-MB-231 breast cancer cells, as compared to normal MCF-10A epithelial breast cells.
机译：描述了涂覆有刺激响应的基于核酸的聚丙烯酰胺水凝胶的负载阿霉素的金属-有机骨架纳米颗粒（NMOF）的合成。水凝胶的形成是通过两条聚丙烯酰胺链P-A和P-B的交联来刺激的，两条链利用链诱导的杂交链反应被两个核酸发夹（4）和（5）官能化。所得的双链桥接聚丙烯酰胺水凝胶以笼状构型包含抗ATP（三磷酸腺苷）适体序列。封装在NMOF中的药物被水凝胶涂层锁定。在癌细胞中过表达的ATP存在下，水凝胶涂层会通过ATP-适体复合物的形成而降解，从而导致阿霉素药物的释放。除了引入合成载有药物的刺激响应性核酸基聚丙烯酰胺水凝胶涂层的NMOFs杂化物的一般方法外，功能化的NMOF还解决了与最近报道的载有核酸的药物加载的NMOFs相关的重大限制。这项研究表明，与核酸门控的NMOF相比，水凝胶涂覆的NMOF中药物的载量高得多，并且克服了核酸保护的NMOF所观察到的药物的非特异性渗漏。与正常的MCF-10A上皮性乳腺癌细胞相比，阿霉素负载的ATP响应水凝胶包被的NMOF对MDA-MB-231乳腺癌细胞具有选择性和有效的细胞毒性。

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