Nafee Noha, Gouda Noha
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria. Egypt.
Curr Gene Ther. 2017;17(2):154-169. doi: 10.2174/1566523217666170510155803.
The restless endeavors revealing the molecular pathways underlying many neurodegenerative diseases and brain tumors have paved the way for the introduction of the selective exogenous gene-based therapeutics. The implicated active biomolecules encompass mainly negatively-charged nucleic acids ranging from DNA, mRNA, non-coding RNAs (small-interfering RNA, siRNA, and microRNA, miRNA), to antisense oligonucleotides. They selectively interfere with the genes translational and/or transcriptional processes. Although many reviews previously addressed brain targeting, a thorough correlation between the molecular properties of these biomacromolecules, the nature of blood brain barrier (BBB) in the accompanying pathological condition, the intracellular targets, as well as the design of the delivery system which will transport the bioactive cargo to the target cells attempting efficient delivery to the active sites in the brain will be appraised. In this review, we will further discuss the tremendous advances in non-viral gene delivery nanosystems currently investigated (starting from self-assembled nanoplexes using cationic polymers or lipids and going through liposomes, aptamers, polymersomes, exosomes, dendrimers and nanoparticles). Unlike previous reviews on this topic, functionalization strategies of the nanocarriers promoting either surface receptor binding or intracellular targeting of the cranial cells will be highlighted, with special emphasis on tailoring smart nanomedicines according to the CNS disease condition. In addition, newly-developed evaluation approaches, cell culture models studying BBB permeability and manipulation of the barrier function of the brain via focused ultrasound will be addressed.
对揭示许多神经退行性疾病和脑肿瘤潜在分子途径的不懈努力，为引入基于选择性外源基因的疗法铺平了道路。涉及的活性生物分子主要包括带负电荷的核酸，从DNA、mRNA、非编码RNA（小干扰RNA，siRNA，和微小RNA，miRNA）到反义寡核苷酸。它们选择性地干扰基因的翻译和/或转录过程。尽管之前有许多综述涉及脑靶向，但这些生物大分子的分子特性、伴随病理状况下血脑屏障（BBB）的性质、细胞内靶点以及将生物活性物质运输到靶细胞以试图有效递送至脑内活性位点的递送系统设计之间的全面相关性将得到评估。在本综述中，我们将进一步讨论目前正在研究的非病毒基因递送纳米系统的巨大进展（从使用阳离子聚合物或脂质的自组装纳米复合物开始，到脂质体、适体、聚合物囊泡、外泌体、树枝状大分子和纳米颗粒）。与以往关于该主题的综述不同，将重点介绍促进纳米载体与表面受体结合或对颅细胞进行细胞内靶向的功能化策略，特别强调根据中枢神经系统疾病状况定制智能纳米药物。此外，还将讨论新开发的评估方法、研究血脑屏障通透性的细胞培养模型以及通过聚焦超声对脑屏障功能的操纵。
