Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.
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DOI:
10.1016/j.nano.2014.01.003
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发表时间:
2014-10
影响因子:
5.4
通讯作者:
Mohapatra, Subhra
Mohapatra, Subhra
中科院分区:
医学2区
文献类型:
--
作者:
Das, Mahasweta;Wang, Chunyan;Bedi, Raminder;Mohapatra, Shyam S.;Mohapatra, Subhra

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创伤性脑损伤 (TBI) 会导致严重死亡、长期残疾和心理症状。基因疗法是治疗不同病理状况的一种有前景的方法。在这里,我们测试了壳聚糖和聚乙烯亚胺 (PEI) 涂层的磁性胶束(CPmag 胶束或 CPMM)(一种潜在的 MRI 造影剂),以在轻度 TBI (mTBI) 后将报告 DNA 传递到大脑。雄性 SD 大鼠在 mTBI 或假手术后立即鼻内施用 CPMM - 表达红色荧光蛋白 (RFP) 的番茄质粒 (ptd) 缀合物。 mTBI 后伊文思蓝外渗表明 CPMM-ptd 通过受损的血脑屏障进入大脑。磁转染增加了大脑中 CPMM 的浓度。 mTBI 后 48 小时,在大脑(皮质和海马)、肺和肝脏中观察到 RFP 表达。 CPMM本身不引起任何炎症反应,并被排出体外。这些结果表明使用鼻内施用 CPMM 作为 mTBI 治疗诊断载体的可能性。
Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CPmag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM - tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 hours after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI.
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