Engineered drug-protein nanoparticle complexes for folate receptor targeting.
Engineered drug-protein nanoparticle complexes for folate receptor targeting.
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DOI：
10.1016/j.bej.2013.09.008
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发表时间：
2014-08-15
影响因子：
3.9
通讯作者：
Wang, Szu-Wen
中科院分区：
文献类型：
--
作者：
Ren, Dongmei;Kratz, Felix;Wang, Szu-Wen
用于治疗应用的纳米材料需要高度的均匀性和功能性，这可能难以实现。一种制造策略是利用重组合成提供的生物精确度。通过蛋白质工程，我们使用丙酮酸脱氢酶的热稳定性E2亚基作为支架生产了~27 nm的十二面体蛋白质纳米颗粒，并增加了光学成像、药物递送和肿瘤靶向能力。将工程化笼状蛋白支架（E2变体D381 C）的内腔中的半胱氨酸与带有马来酰亚胺的Alexa Fluor 532（AF 532）和多柔比星（DOX）缀合。外表面用单独的聚乙二醇（PEG）或通过PEG接头用肿瘤靶向配体叶酸（FA）官能化。所得的双功能纳米颗粒保持完整并正确组装。过表达叶酸受体的细胞对FA展示纳米颗粒（D381 C-AF 532-PEG-FA）的摄取比非靶向纳米颗粒（D381 C-AF 532-PEG）高约6倍，并且被证实是FA特异性的。含有DOX的纳米颗粒在低微摩尔范围内都具有细胞毒性。据我们所知，这项工作是第一次将酸不稳定药物释放和叶酸受体靶向同时整合到重组蛋白纳米颗粒上，它展示了使用生物纤维素策略产生功能性纳米材料的潜力。
Nanomaterials that are used in therapeutic applications need a high degree of uniformity and functionality which can be difficult to attain. One strategy for fabrication is to utilize the biological precision afforded by recombinant synthesis. Through protein engineering, we have produced ~27-nm dodecahedral protein nanoparticles using the thermostable E2 subunit of pyruvate dehydrogenase as a scaffold and added optical imaging, drug delivery, and tumor targeting capabilities. Cysteines in the internal cavity of the engineered caged protein scaffold (E2 variant D381C) were conjugated with maleimide-bearing Alexa Fluor 532 (AF532) and doxorubicin (DOX). The external surface was functionalized with polyethylene glycol (PEG) alone or with the tumor-targeting ligand folic acid (FA) through a PEG linker. The resulting bi-functional nanoparticles remained intact and correctly assembled. The uptake of FA-displaying nanoparticles (D381C-AF532-PEG-FA) by cells overexpressing the folate receptor was approximately six times greater than of non-targeting nanoparticles (D381C-AF532-PEG) and was confirmed to be FA-specific. Nanoparticles containing DOX were all cytotoxic in the low micromolar range. To our knowledge, this work is the first time that acid-labile drug release and folate receptor targeting have been simultaneously integrated onto recombinant protein nanoparticles, and it demonstrates the potential of using biofabrication strategies to generate functional nanomaterials.
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DOI：
10.1083/jcb.200910104
发表时间：
2010-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ruoslahti E;Bhatia SN;Sailor MJ
通讯作者：
Sailor MJ
影响因子：
13.3
作者：
Ren, Dongmei;Kratz, Felix;Wang, Szu-Wen
通讯作者：
Wang, Szu-Wen
影响因子：
6.2
作者：
Molino, Nicholas M.;Bilotkach, Kateryna;Wang, Szu-Wen
通讯作者：
Wang, Szu-Wen
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.
影响因子：
15
作者：
Bharali, DJ;Lucey, DW;Prasad, PN
通讯作者：
Prasad, PN