Radiolytic Reduction Characteristics of Drug-Encapsulating DNA Aggregates Possessing Disulfide Bond
Radiolytic Reduction Characteristics of Drug-Encapsulating DNA Aggregates Possessing Disulfide Bond
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DOI：
10.1021/bc3002985
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发表时间：
2012-09-01
影响因子：
4.7
通讯作者：
Nishimoto, Sei-ichi
中科院分区：
文献类型：
--
作者：
Tanabe, Kazuhito;Asada, Takumi;Nishimoto, Sei-ichi
展示了由人工DNA组成的辐射响应聚集体。我们制备了以寡核苷酸(ODN)为亲水部分、烷基链为疏水部分的DNA两亲分子(DAMs)，它们之间通过辐射敏感的二硫键相连。水坝在水溶液中聚集成纳米级的聚集体，包裹着疏水染料和药物。X-射线在大坝中引发了二硫键的选择性还原，引发了交换反应，导致聚集体解离并释放出包裹的染料和药物。在本研究合成的DAM1中，含有5聚ODN的DAM1具有良好的纳米载体性能，例如，大量的药物被包裹在由DAM1组成的聚集体中，并且聚集体对辐射还原表现出很高的敏感性。用活的A549细胞进行的生物实验表明，聚集体顺利地渗透到细胞内，而不需要转染剂，而聚集体内的药物由于包裹而是惰性的。由于聚集体的解离和药物的释放，X-射线增强了细胞毒性。
Radiation-responsive aggregates consisting of artificial DNA were demonstrated. We prepared DNA amphiphiles (DAMs) consisting of oligodeoxynucleotides (ODNs) as the hydrophilic part and an alkyl chain as the hydrophobic part, which were linked by a radiation-sensitive disulfide bond. DAMs assembled to form nanosized aggregates in aqueous solution that encapsulated hydrophobic dyes and drugs. X-irradiation, which triggered selective reduction at the disulfide bond in the DAMs, induced an exchange reaction, resulting in dissociation of the aggregates and release of encapsulated dyes and drugs. Among the DAMs synthesized in this study, DAM 1 possessing 5 mer ODNs showed favorable properties as a nanocarrier; for example, the large amount of drug was encapsulated in the aggregates consisting of DAM 1, and the aggregates showed the high sensitivity to radiolytic reduction. Biological experiments using living A549 cells revealed that the aggregates smoothly penetrated into the cells without the need for transfection reagents, while the drugs inside the aggregates were inert because of the encapsulation. X-irradiation enhanced the cytotoxicity because of dissociation of the aggregates and concomitant release of drugs.