A novel local anti-colorectal cancer drug delivery system: negative lipidoid nanoparticles with a passive target via a size-dependent pattern
A novel local anti-colorectal cancer drug delivery system: negative lipidoid nanoparticles with a passive target via a size-dependent pattern
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一种新型局部抗结直肠癌药物递送系统：通过尺寸依赖性模式具有被动靶点的负类脂质纳米颗粒
DOI：
10.1088/0957-4484/24/37/375101
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发表时间：
2013-09-20
期刊：
影响因子：
3.5
通讯作者：
Wang, Huimin
中科院分区：
文献类型：
--
作者：
Ding, Weifeng;Wang, Feng;Wang, Huimin
核酸药物的无毒、靶向和有效递送仍然是临床开发的重要挑战。在这里，我们描述了一种新的负性类胡萝卜素纳米颗粒递送系统，提供了基于包埋的转染剂，用于将siRNA局部递送到结直肠癌病灶。该给药系统由类环糊精材料98 N12 -5（1）、mPEG 2000-C12/C14甘油酯和胆固醇按所需摩尔比合成，实现颗粒表面带阴离子电荷，可在较大程度上缓解机体的炎症反应和免疫刺激，体现出显著的生物相容性。特别地，选择mPEG 2000-C12/C14甘油酯以改善递送系统的稳定性和通过延长碳的尾部长度来保护核酸，这对于中和98 N12 -5（1）的正电荷以形成所得阴离子颗粒也是至关重要的。体内实验表明，90 nm的粒径以尺寸依赖性方式完美地实现了被动靶点，并且通过局部递送方法（灌肠）不影响肝脏和肾脏的功能。我们阐明了阴性类胡萝卜素纳米粒的摄取通过脂筏内吞途径内化，具有低细胞毒性、强生物相容性和高疗效。本研究表明，阴性艾司氯胺酮纳米粒灌肠给药系统是一种独特且合适的局部抗结直肠癌核酸药物给药平台，类似模式的应用在其他治疗环境中也是可行的。
The nontoxic, targeted and effective delivery of nucleic acid drugs remains an important challenge for clinical development. Here, we describe a novel negative lipidoid nanoparticle delivery system, providing entrapment-based transfection agents for local delivery of siRNA to the colorectal cancer focus. The delivery system was synthesized with lipidoid material 98N12-5(1), mPEG2000-C12/C14 glyceride and cholesterol at a desired molar ratio to realize the anionic surface charge of particles, which could alleviate to a larger degree the inflammatory response and immune stimulation of the organism, embodying dramatic biocompatibility. In particular, mPEG2000-C12/C14 glyceride was selected to ameliorate the stability of the delivery system and protection of nucleic acids by extending the tail length of the carbons, crucial also to neutralize the positive charge of 98N12-5(1) to form a resultant anionic particle. In vivo experiments revealed that a particle size of 90 nm perfectly realized a passive target in a size-dependent manner and did not affect the function of the liver and kidneys by a local delivery method, enema. We clarified that the uptake of negative lipidoid nanoparticles internalized through a lipid raft endocytotic pathway with low cytotoxicity, strong biocompatibility and high efficacy. This study suggests that negative lipidoid nanoparticles with enema delivery costitute, uniquely and appropriately, a local anti-colorectal cancer nucleic acid drug delivery platform, and the application of similar modes may be feasible in other therapeutic settings.