Department of Chemical Engineering and Materials Science, University of California, Irvine, 92697, USA.
Adv Drug Deliv Rev. 2012 Aug;64(11):1046-59. doi: 10.1016/j.addr.2012.01.018. Epub 2012 Feb 4.
Multiple extra- and intracellular obstacles, including low stability in blood, poor cellular uptake, and inefficient endosomal escape and disassembly in the cytoplasm, have to be overcome in order to deliver nucleic acids for gene therapy. This review introduces the recent advances in tackling the key challenges in achieving efficient, targeted, and safe nonviral gene delivery using various nucleic acid-containing nanomaterials that are designed to respond to various extra- and intracellular biological stimuli (e.g., pH, redox potential, and enzyme) as well as external artificial triggers (e.g., light and ultrasound). Gene delivery in combination with molecular imaging and targeting enables diagnostic assessment, treatment monitoring and quantification of efficiency, and confirmation of cure, thus fulfilling the great promise of efficient and personalized medicine. Nanomaterials platform for combined imaging and gene therapy, nanotheragnostics, using stimuli-responsive materials is also highlighted in this review. It is clear that developing novel multifunctional nonviral vectors, which transform their physico-chemical properties in response to various stimuli in a timely and spatially controlled manner, is highly desired to translate the promise of gene therapy for the clinical success.
为了将核酸用于基因治疗，必须克服多种细胞内外的障碍，包括在血液中的稳定性低、细胞摄取效率低、以及在细胞质中有效的内体逃逸和解体。本综述介绍了使用各种含核酸的纳米材料克服实现高效、靶向和安全的非病毒基因传递的关键挑战的最新进展，这些纳米材料的设计旨在响应各种细胞外和细胞内的生物刺激（例如 pH 值、氧化还原电位和酶）以及外部人工触发（例如光和超声）。基因传递与分子成像和靶向相结合，能够进行诊断评估、治疗监测和效率量化以及治愈确认，从而实现高效和个性化医疗的巨大承诺。本综述还强调了使用刺激响应材料的用于联合成像和基因治疗的纳米材料平台，即纳米诊断学。显然，开发新型多功能非病毒载体，使其能够及时和空间控制的方式响应各种刺激改变其物理化学性质，对于将基因治疗的前景转化为临床成功是非常需要的。
