RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors.

RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors.
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DOI:
10.1021/nn305791q
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发表时间:
2013-06-25
期刊:
影响因子:
17.1
通讯作者:
Xie, Jin
Xie, Jin
中科院分区:
材料科学1区
文献类型:
--
作者:
Zhen, Zipeng;Tang, Wei;Chen, Hongmin;Lin, Xin;Todd, Trever;Wang, Geoffrey;Cowger, Taku;Chen, Xiaoyuan;Xie, Jin

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铁蛋白是在人类和大多数生物体中发现的主要铁储存蛋白。每个铁蛋白由24个亚基组成,它们自组装形成笼状纳米结构。FRT纳米笼可以被遗传修饰以在表面上呈现肽序列。最近,我们证明了Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys(RGD 4C)修饰的铁蛋白可以通过RGD整合素αvβ3相互作用有效地归巢肿瘤。虽然有前途,但评价表面修饰的铁蛋白纳米笼作为药物载体的研究很少报道。在此,我们表明,在与Cu(II)预络合后,阿霉素可以以高效率(高达73.49wt%)负载到RGD修饰的脱铁铁蛋白纳米笼上。当在U87 MG皮下肿瘤模型上进行研究时,这些负载多柔比星的铁蛋白纳米笼显示出比游离多柔比星更长的循环半衰期、更高的肿瘤摄取、更好的肿瘤生长抑制和更少的心脏毒性。这种技术可以扩展到加载广泛的治疗方法,并在临床转化中具有巨大的潜力。
Ferritin is a major iron storage protein found in humans and most living organisms. Each ferritin is comprised of 24 subunits, which self-assemble to form a cage-like nanostructure. FRT nanocages can be genetically modified to present a peptide sequence on the surface. Recently, we demonstrated that Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys (RGD4C)-modified ferritin can efficiently home to tumors through RGD integrin αvβ3 interaction. Though promising, studies on evaluating surface modified ferritin nanocages as drug delivery vehicles have seldom been reported. Herein we showed that after being pre-complexed with Cu(II), doxorubicin can be loaded onto RGD modified apoferritin nanocages with high efficiency (up to 73.49wt%). When studied on U87MG subcutaneous tumor models, these doxorubicin-loaded ferritin nanocages showed a longer circulation half-life, higher tumor uptake, better tumor growth inhibition, and less cardiotoxicity than free doxorubicin. Such a technology might be extended to load a broad range of therapeutics and holds great potential in clinical translation.
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