Engineering of targeted nanoparticles for cancer therapy using internalizing aptamers isolated by cell-uptake selection.
Engineering of targeted nanoparticles for cancer therapy using internalizing aptamers isolated by cell-uptake selection.
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DOI：
10.1021/nn204165v
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发表时间：
2012-01-24
期刊：
影响因子：
17.1
通讯作者：
Farokhzad OC
中科院分区：
文献类型：
--
作者：
Xiao Z;Levy-Nissenbaum E;Alexis F;Lupták A;Teply BA;Chan JM;Shi J;Digga E;Cheng J;Langer R;Farokhzad OC
开发用于癌症治疗的靶向纳米颗粒（NP）的主要挑战之一是发现允许靶向癌细胞的差异结合和摄取的靶向配体。使用前列腺癌（PCa）作为模型疾病，我们开发了细胞摄取选择策略以分离用于NP掺入的PCa特异性内化2 '-Omethyl RNA适体（Apts）。进行12个循环的选择和反选择以获得一组内化Apt，其可以将PCa细胞与非前列腺和正常前列腺细胞区分开。在Apt表征、尺寸最小化和Apt与荧光标记的聚合物NP的缀合之后，当与缺乏内化Apt的非靶向NP相比时，NP-Apt生物缀合物表现出PCa特异性和细胞摄取的增强。此外，当多西他赛（一种用于治疗PCa的化疗剂）包封在NP-Apt内时，在靶向PCa细胞中实现了细胞毒性的显著改善。我们的选择策略不是像以前的选择过程中报道的那样分离高亲和力Apt，而是设计成富集癌细胞特异性内化Apt。类似的细胞摄取选择策略可用于开发针对无数其他疾病的特异性内化配体，并且可以潜在地促进将各种分子（包括药物和siRNA）递送到细胞中。
One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate cancer (PCa) as a model disease, we developed a cell-uptake selection strategy to isolate PCa-specific internalizing 2'-Omethyl RNA aptamers (Apts) for NP incorporation. Twelve cycles of selection and counter-selection were done to obtain a panel of internalizing Apts, which can distinguish PCa cells from non-prostate and normal prostate cells. After Apt characterization, size minimization, and conjugation of the Apts with fluorescently-labeled polymeric NPs, the NP-Apt bioconjugates exhibit PCa specificity and enhancement in cellular uptake when compared to non-targeted NPs lacking the internalizing Apts. Furthermore, when docetaxel, a chemotherapeutic agent used for the treatment of PCa, was encapsulated within the NP-Apt, a significant improvement in cytotoxicity was achieved in targeted PCa cells. Rather than isolating high-affinity Apts as reported in previous selection processes, our selection strategy was designed to enrich cancer-cell specific internalizing Apts. A similar cell-uptake selection strategy may be used to develop specific internalizing ligands for a myriad of other diseases and can potentially facilitate delivering various molecules, including drugs and siRNAs, into cells.
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影响因子：
2.8
作者：
O'Keefe, DS;Bacich, DJ;Heston, WDW
通讯作者：
Heston, WDW
影响因子：
16.6
作者：
Cao, Zehui;Tong, Rong;Lu, Yi
通讯作者：
Lu, Yi
DOI：
10.1073/pnas.0601755103
发表时间：
2006-04-18
影响因子：
11.1
作者：
Farokhzad, OC;Cheng, JJ;Langer, R
通讯作者：
Langer, R
影响因子：
--
作者：
Burmeister, PE;Lewis, SD;Keefe, AD
通讯作者：
Keefe, AD
DOI：
10.1073/pnas.2136683100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Daniels, DA;Chen, H;Gold, L
通讯作者：
Gold, L