School of Chemical Engineering, The University of Adelaide, Adelaide, SA5005, Australia.
Adv Healthc Mater. 2014 Nov;3(11):1839-48. doi: 10.1002/adhm.201400187. Epub 2014 Jun 26.
Gene therapy presents a unique opportunity for the treatment of genetic diseases, but the lack of multifunctional delivery systems has hindered its clinical applications. Here, a new delivery vector, autofluorescent polyethyleneimine (PEI) nanogels, for highly efficient and traceable gene delivery is developed. Different from commercial high-molecular-weight PEI, the cationic nanogels are noncytotoxic and able to be fragmented due to their unique intracellular microenvironment-responsive structures. The biodegradable nanogels can effectively load plasmid DNA (pDNA), and the self-assembled polyplexes can be cleaved after cellular uptake to improve gene transfection efficiency. Most importantly, the nanogels and the nanogel/pDNA polyplexes are autofluorescent. The fluorescence is stable in blood plasma and responsive to the intracellular microenvironment. The breakup of the nanogels or polyplexes leads to the loss of fluorescence, and thus the gene delivery and carrier biodegradation processes can be monitored. The reported multifunctional system demonstrates excellent biocompatibility, high transfection efficiency, responsive biodegradability, controlled gene release, label-free and simultaneous fluorescence tracking, which will provide a new platform for future scientific investigation and practical implications in gene therapy.
基因治疗为治疗遗传疾病提供了独特的机会，但多功能输送系统的缺乏阻碍了其临床应用。在这里，开发了一种新的输送载体，即自发荧光聚乙烯亚胺（PEI）纳米凝胶，用于高效和可追踪的基因输送。与商业高分子量 PEI 不同，由于其独特的细胞内微环境响应结构，阳离子纳米凝胶是非细胞毒性的并且能够被碎片化。可生物降解的纳米凝胶可以有效地装载质粒 DNA（pDNA），并且自组装的聚电解质复合物可以在细胞摄取后被切割以提高基因转染效率。最重要的是，纳米凝胶和纳米凝胶/ pDNA 聚电解质复合物具有自发荧光。荧光在血浆中稳定且对细胞内微环境有响应。纳米凝胶或聚电解质复合物的破裂会导致荧光丧失，因此可以监测基因输送和载体生物降解过程。所报道的多功能系统表现出优异的生物相容性、高转染效率、响应性生物降解性、可控基因释放、无标记和荧光同时跟踪，这将为未来的科学研究和基因治疗的实际应用提供新的平台。
