Das Mahasweta, Wang Chunyan, Bedi Raminder, Mohapatra Shyam S, Mohapatra Subhra
USF Morsani College of Medicine, Nanomedicine Research Center, University of South Florida College of Medicine, Tampa, FL, USA; Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
USF Morsani College of Medicine, Nanomedicine Research Center, University of South Florida College of Medicine, Tampa, FL, USA; Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
Nanomedicine. 2014 Oct;10(7):1539-48. doi: 10.1016/j.nano.2014.01.003. Epub 2014 Jan 29.
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 (CP-mag 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 h 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. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body.
创伤性脑损伤（TBI）会导致显著的死亡率、长期残疾和心理症状。基因治疗是治疗不同病理状况的一种有前景的方法。在此，我们测试了壳聚糖和聚乙烯亚胺（PEI）包被的磁性微球（CP-磁性微球或CPMMs），一种潜在的MRI造影剂，在轻度创伤性脑损伤（mTBI）后将报告基因DNA递送至大脑。在雄性SD大鼠中，mTBI或假手术后立即经鼻给予表达红色荧光蛋白（RFP）的CPMM-番茄质粒（ptd）偶联物。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CPMMs的浓度。mTBI后48小时在大脑（皮质和海马体）、肺和肝脏中观察到RFP表达。CPMM本身不会引起任何炎症反应，并可从体内排出。这些结果表明经鼻给予CPMM作为mTBI的治疗诊断载体具有可能性。临床编辑评论：在本研究中，壳聚糖和PEI包被的磁性微球（CPMM）在啮齿动物模型的创伤性脑损伤中被证明是潜在有用的载体。磁转染增加了大脑中CPMMs的浓度，经鼻给药后，CPMM不会引起任何炎症反应，并可从体内排出。
