Self-Assembled Redox Dual-Responsive Prodrug-Nanosystem Formed by Single Thioether-Bridged Paclitaxel-Fatty Acid Conjugate for Cancer Chemotherapy.
Self-Assembled Redox Dual-Responsive Prodrug-Nanosystem Formed by Single Thioether-Bridged Paclitaxel-Fatty Acid Conjugate for Cancer Chemotherapy.
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用于癌症化疗的单硫醚桥紫杉醇-脂肪酸缀合物形成的自组装氧化还原双响应前药纳米系统
DOI：
10.1021/acs.nanolett.6b01632
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发表时间：
2016-09-14
期刊：
影响因子：
10.8
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Luo C;Sun J;Liu D;Sun B;Miao L;Musetti S;Li J;Han X;Du Y;Li L;Huang L;He Z
通过开发具有高载药量和智能刺激触发的肿瘤细胞药物释放的纳米微粒给药系统(Nano-DDS)，可以极大地提高化疗效果。在这里，我们报道了一种由紫杉醇(PTX)和油酸(OA)的疏水性小分子偶联物自组装的新型氧化还原双响应型前药纳米系统。硫醚连接的偶联物(Ptx-S-OA)和二硫代醚插入的偶联物(Ptx-2S-OA)被设计用于响应肿瘤中的氧化还原异质性。二硫代醚已被报道表现出氧化还原双重反应，但我们发现PTX-S-OA表现出比PTX-2S-OA更好的氧化还原敏感性，实现了更快和更有选择性地从氧化还原刺激触发的前药纳米组件中释放游离PTX。聚乙二醇化的PTX-S-OA纳米组件具有惊人的高载药量(57.4%)，在人表皮样癌异种移植瘤中显示出强大的抗肿瘤活性。这种新型的前药纳米系统解决了PTX疏水前药载药量低和药物释放效率低的问题，并为开发高效抗癌药物输送的氧化还原双重敏感偶联物或聚合物提供了可能性。
Chemotherapeutic efficacy can be greatly improved by developing nanoparticulate drug delivery systems (nano-DDS) with high drug loading capacity and smart stimulus-triggered drug release in tumor cells. Herein, we report a novel redox dual-responsive prodrug-nanosystem self-assembled by hydrophobic small-molecule conjugates of paclitaxel (PTX) and oleic acid (OA). Thioether linked conjugates (PTX-S-OA) and dithioether inserted conjugates (PTX-2S-OA) are designed to respond to the redox-heterogeneity in tumor. Dithioether has been reported to show redox dual-responsiveness, but we find that PTX-S-OA exhibits superior redox sensitivity over PTX-2S-OA, achieving more rapid and selective release of free PTX from the prodrug nanoassemblies triggered by redox stimuli. PEGylated PTX-S-OA nanoassemblies, with impressively high drug loading (57.4%), exhibit potent antitumor activity in a human epidermoid carcinoma xenograft. This novel prodrug-nanosystem addresses concerns related to the low drug loading and inefficient drug release from hydrophobic prodrugs of PTX, and provides possibilities for the development of redox dual-sensitive conjugates or polymers for efficient anticancer drug delivery.
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影响因子：
46.2
作者：
Karimi M;Ghasemi A;Sahandi Zangabad P;Rahighi R;Moosavi Basri SM;Mirshekari H;Amiri M;Shafaei Pishabad Z;Aslani A;Bozorgomid M;Ghosh D;Beyzavi A;Vaseghi A;Aref AR;Haghani L;Bahrami S;Hamblin MR
通讯作者：
Hamblin MR
影响因子：
14
作者：
Du, Xiao-Jiao;Wang, Ji-Long;Wang, Jun
通讯作者：
Wang, Jun
影响因子：
50.5
作者：
Bedikian, A. Y.;DeConti, R. C.;Ernstoff, M.
通讯作者：
Ernstoff, M.
影响因子：
4.5
作者：
Aslan B;Ozpolat B;Sood AK;Lopez-Berestein G
通讯作者：
Lopez-Berestein G
影响因子：
10.8
作者：
Shi J;Votruba AR;Farokhzad OC;Langer R
通讯作者：
Langer R