Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord.
Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord.
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DOI：
10.1016/j.jconrel.2013.03.009
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发表时间：
2013-06-10
期刊：
影响因子：
--
通讯作者：
Milligan ED
中科院分区：
文献类型：
--
作者：
Dengler EC;Liu J;Kerwin A;Torres S;Olcott CM;Bowman BN;Armijo L;Gentry K;Wilkerson J;Wallace J;Jiang X;Carnes EC;Brinker CJ;Milligan ED
无定形介孔二氧化硅纳米颗粒（“原细胞”），支持表面脂质双层最近在体外表征为载体构建体的小药物和DNA的交付，在这里报道为高度生物相容性在体外和体内，涉及脑和脊髓后，脊髓交付到腰骶蛛网膜下腔（鞘内; i.t.）。具体地，带正电荷的1，2-二油酰基-3-三甲基铵-丙烷（DOTAP）-胆固醇（DOTAP：Chol）脂质体配制的原细胞显示稳定的体外货物释放动力学和细胞白介素-10（IL-10）转基因转染。使用合成的非病毒载体平台将疼痛抑制治疗性转基因IL-10递送至脊髓蛛网膜下腔的最新方法在周围神经病变的动物模型中产生了有希望的结果，周围神经病变是一种涉及神经系统中感觉通路内异常神经元通信的病症。非病毒药物和基因递送原始细胞平台提供了潜在的灵活性，因为货物释放速率可以是pH依赖性的。我们在这里报告说，递送具有支持DOTAP：Chol脂质体表面涂层并含有IL-10转基因的改良化学性质的原始细胞，导致大鼠中疼痛相关行为的功能性抑制持续较长时间。这项研究是第一次证明，原始细胞载体提供了顺从和持久的体内生物学特性，可应用于脊髓基因传递。
Amorphous mesoporous silica nanoparticles (‘protocells’) that support surface lipid bilayers recently characterized in vitro as carrier constructs for small drug and DNA delivery are reported here as highly biocompatible both in vitro and in vivo, involving the brain and spinal cord following spinal delivery into the lumbosacral subarachnoid space (intrathecal; i.t.). Specifically, positively charged, 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP) -cholesterol (DOTAP:Chol) liposome-formulated protocells revealed stable in vitro cargo release kinetics and cellular interleukin-10 (IL-10) transgene transfection. Recent approaches using synthetic non-viral vector platforms to deliver the pain-suppressive therapeutic transgene, IL-10, to the spinal subarachnoid space has yielded promising results in animal models of peripheral neuropathy, a condition involving aberrant neuronal communication within sensory pathways in the nervous system. Non-viral drug and gene delivery protocell platforms offer potential flexibility because cargo release-rates can be pH-dependent. We report here that i.t. delivery of protocells, with modified chemistry supporting a surface coating of DOTAP:Chol liposomes and containing the IL-10 transgene, results in functional suppression of pain-related behavior in rats for extended periods. This study is the first demonstration that protocell vectors offer amenable and enduring in vivo biological characteristics that can be applied to spinal gene delivery.
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影响因子：
5.3
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