Rajendrakumar Santhosh Kalash, Uthaman Saji, Cho Chong Su, Park In-Kyu
Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 61469, Korea.
Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea.
Nanomaterials (Basel). 2017 May 26;7(6):120. doi: 10.3390/nano7060120.
In the current era of gene delivery, trigger-responsive nanoparticles for the delivery of exogenous nucleic acids, such as plasmid DNA (pDNA), mRNA, siRNAs, and miRNAs, to cancer cells have attracted considerable interest. The cationic gene transporters commonly used are typically in the form of polyplexes, lipoplexes or mixtures of both, and their gene transfer efficiency in cancer cells depends on several factors, such as cell binding, intracellular trafficking, buffering capacity for endosomal escape, DNA unpacking, nuclear transportation, cell viability, and DNA protection against nucleases. Some of these factors influence other factors adversely, and therefore, it is of critical importance that these factors are balanced. Recently, with the advancements in contemporary tools and techniques, trigger-responsive nanoparticles with the potential to overcome their intrinsic drawbacks have been developed. This review summarizes the mechanisms and limitations of cationic gene transporters. In addition, it covers various triggers, such as light, enzymes, magnetic fields, and ultrasound (US), used to enhance the gene transfer efficiency of trigger-responsive gene transporters in cancer cells. Furthermore, the challenges associated with and future directions in developing trigger-responsive gene transporters for anticancer therapy are discussed briefly.
在当前的基因递送时代，用于将外源核酸（如质粒DNA（pDNA）、mRNA、小干扰RNA（siRNAs）和微小RNA（miRNAs））递送至癌细胞的触发响应型纳米颗粒已引起了广泛关注。常用的阳离子基因转运体通常呈多聚体、脂质体或两者混合物的形式，它们在癌细胞中的基因转移效率取决于多个因素，如细胞结合、细胞内运输、内体逃逸的缓冲能力、DNA解包、核运输、细胞活力以及DNA对核酸酶的保护作用。其中一些因素会对其他因素产生不利影响，因此，平衡这些因素至关重要。近年来，随着现代工具和技术的进步，已开发出具有克服其固有缺点潜力的触发响应型纳米颗粒。本综述总结了阳离子基因转运体的机制和局限性。此外，还涵盖了各种触发因素，如光、酶、磁场和超声（US），这些因素用于提高触发响应型基因转运体在癌细胞中的基因转移效率。此外，还简要讨论了开发用于抗癌治疗的触发响应型基因转运体所面临的挑战和未来方向。
