Linearized oncolytic adenoviral plasmid DNA delivered by bioreducible polymers.
Linearized oncolytic adenoviral plasmid DNA delivered by bioreducible polymers.
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DOI：
10.1016/j.jconrel.2011.12.008
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发表时间：
2012-03-28
期刊：
影响因子：
--
通讯作者：
Kim SW
中科院分区：
文献类型：
--
作者：
Kim J;Kim PH;Nam HY;Lee JS;Yun CO;Kim SW
为了克服腺病毒（Ad）作为肿瘤治疗的系统性递送载体的局限性，我们开发了一种新的系统，其使用溶瘤Ad质粒DNA与两种生物可还原聚合物：甘氨酸接枝的生物可还原聚（二硫胺）聚合物（ABP）和PEG 5 k缀合的ABP（ABP 5 k），期望通过子代病毒产生随后复制引起溶瘤效果。与每种聚合物复合的线性化病毒复制用Ad DNA仅能在人癌细胞中复制并产生子代病毒。递送DNA的非免疫原性聚合物显著地引起逃避先天性和适应性免疫应答。与裸Ad相比，全身施用的复合物在肝脏中的生物分布率降低约99%。此外，ABP或ABP 5 k递送的Ad DNA的肿瘤-肝脏比分别比裸Ad高229倍或419倍。ABP 5 k提高了DNA定位在肿瘤内的机会，与肝脏相比，比率增加了1.8倍。总之，用于递送具有生物可还原聚合物的溶瘤Ad质粒DNA的创新且简单的系统，跳过诸如溶瘤Ad载体的生成和表征的耗时步骤，可以用作癌症治疗的替代方法。
As an effort to overcome limits of adenovirus (Ad) as a systemic delivery vector for cancer therapy, we developed a novel system using oncolytic Ad plasmid DNA with two bioreducible polymers: arginine-grafted bioreducible poly(disulfide amine)polymer (ABP) and PEG5k-conjugated ABP (ABP5k) in expectation of oncolytic effect caused by progeny viral production followed by replication. The linearized Ad DNAs for active viral replication polyplexed with each polymer were able to replicate only in humancancer cells and produce progeny viruses. The non-immunogenic polymers delivering the DNAs markedly elicited to evade the innate and adaptive immune response. The biodistribution ratio of the polyplexes administered systemically was approximately 99% decreased in liver when compared with naked Ad. Moreover, tumor-to-liver ratio of the Ad DNA delivered by ABP or ABP5k was significantly elevated at 229- or 419-fold greater than that of naked Ad, respectively. The ABP5k improved the chance of the DNA to localize within tumor versus liver with 1.8-fold increased ratio. In conclusion, the innovative and simple system for delivering oncolytic Ad plasmid DNA with the bioreducible polymers, skipping time-consuming steps such as generation and characterization of oncolytic Ad vectors, can be utilized as an alternative approach for cancer therapy.
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影响因子：
10.8
作者：
Kwon, Oh-Joon;Kang, Eunah;Yun, Chae-Ok
通讯作者：
Yun, Chae-Ok
影响因子：
10.8
作者：
Jung, Yukyung;Park, Hyo-Jin;Haam, Seungjoo
通讯作者：
Haam, Seungjoo
影响因子：
4.2
作者：
Muruve, DA;Barnes, MJ;Libermann, TA
通讯作者：
Libermann, TA
影响因子：
14
作者：
Kim, Jaesung;Nam, Hye Yeong;Kim, Tae-il;Kim, Pyung-Hwan;Ryu, Jihoon;Yun, Chae-Ok;Kim, Sung Wan
通讯作者：
Kim, Sung Wan
影响因子：
3.7
作者：
Fischer, D;Bieber, T;Kissel, T
通讯作者：
Kissel, T