Cell targeting with hybrid Qβ virus-like particles displaying epidermal growth factor.
Cell targeting with hybrid Qβ virus-like particles displaying epidermal growth factor.
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DOI：
10.1002/cbic.201100469
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发表时间：
2011-11-04
期刊：
影响因子：
3.2
通讯作者：
Finn, M. G.
中科院分区：
文献类型：
--
作者：
Pokorski, Jonathan K.;Hovlid, Marisa L.;Finn, M. G.
来自病毒衣壳蛋白的自组装的结构均匀的蛋白质纳米颗粒是用于纳米医学的细胞靶向基序的多价展示的有吸引力的平台。基于病毒的纳米颗粒特别令人感兴趣，因为支架可以通过遗传和化学方法操纵，以同时显示靶向基团并携带功能性有效载荷。在这里，我们展示了人表皮生长因子（EGF）在噬菌体Qβ的外表面作为一个C-末端基因融合的Qβ衣壳蛋白。野生型Qβ和EGF修饰的亚基的共组装导致结构均匀的纳米颗粒在其外表面上显示5至12个EGF拷贝。发现这些颗粒可通过标准方法以及高保真铜催化的叠氮化物-炔环加成反应（CuAAC）进行生物缀合。这种化学衍生作用不会损害颗粒与EGF受体特异性相互作用的能力。此外，颗粒展示的EGF保持生物活性，促进EGF受体的自磷酸化和A431细胞的凋亡。这些结果表明，混合Qβ-EGF纳米颗粒可能是有用的载体，用于成像和/或治疗剂的靶向递送。
Structurally uniform protein nanoparticles derived from the self-assembly of viral capsid proteins are attractive platforms for the multivalent display of cell-targeting motifs for use in nanomedicine. Virus-based nanoparticles are of particular interest because the scaffold can be manipulated both genetically and chemically to simultaneously display targeting groups and carry a functional payload. Here, we displayed the human epidermal growth factor (EGF) on the exterior surface of bacteriophage Qβ as a C-terminal genetic fusion to the Qβ capsid protein. The co-assembly of wild-type Qβ and EGF-modified subunits resulted in structurally homogeneous nanoparticles displaying between 5 and 12 copies of EGF on their exterior surface. The particles were found to be amenable to bioconjugation via standard methods as well as the high-fidelity copper catalyzed azide-alkyne cycloaddition reaction (CuAAC). Such chemical derivatization did not impair the ability of the particles to specifically interact with the EGF receptor. Additionally, the particle-displayed EGF remained biologically active promoting auto-phosphorylation of the EGF receptor and apoptosis of A431 cells. These results suggest that hybrid Qβ-EGF nanoparticles could be useful vehicles for targeted delivery of imaging and/or therapeutic agents.
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影响因子：
17.1
作者：
Bhirde, Ashwin A.;Patel, Vyomesh;Gavard, Julie;Zhang, Guofeng;Sousa, Alioscka A.;Masedunskas, Andrius;Leapman, Richard D.;Weigert, Roberto;Gutkind, J. Silvio;Rusling, James F.
通讯作者：
Rusling, James F.
影响因子：
4.7
作者：
Beuttler, Julia;Rothdiener, Miriam;Kontermann, Roland E.
通讯作者：
Kontermann, Roland E.
影响因子：
4.7
作者：
Capala, J;Barth, RF;Carlsson, J
通讯作者：
Carlsson, J
DOI：
10.1073/pnas.1011368107
发表时间：
2010-10-19
影响因子：
11.1
作者：
Kolishetti, Nagesh;Dhar, Shanta;Farokhzad, Omid C.
通讯作者：
Farokhzad, Omid C.
影响因子：
4.7
作者：
Liberelle, Benoit;Boucher, Cyril;De Crescenzo, Gregory
通讯作者：
De Crescenzo, Gregory