Pyykkö Ilmari, Zou Jing, Zhang Weikai, Zhang Ya
Department of Otolaryngology, University of Tampere Medical School, Tampere, Finland.
Curr Opin Otolaryngol Head Neck Surg. 2011 Oct;19(5):388-96. doi: 10.1097/MOO.0b013e32834aa3a8.
The delivery of targetable synthetic vectors that can carry a variety of drugs, proteins, and nucleic acids, such as DNA and small interfering RNA (siRNA), to mammalian cells is important as a potential therapeutic system that avoids the problems that are associated with viruses.
The so-called multifunctional nanocarriers that are equipped with several functions, such as targetability, shelter from the immune system, and opsonization, and are capable of delivering payload across the nuclear envelope, have been synthesized. To improve transfection efficiency, a group of novel peptides have been attached to the surface of the carrier that will enhance endosomal escape and promote nuclear entry. The targeting of tropomyocin receptor kinase B (TrkB) with ligands enhances uptake in spiral ganglion cell culture. Treatment cargos have included growth factors such as the Math-1 gene, short hairpin RNA, and steroids. The problems with current synthetic nanocarriers are poorer selectivity, internalization, and transfection rate compared with viral vectors.
Within a few years, when the synthetic vectors have been optimized, the first human drugs/proteins/gene product-based therapies will become available in a phase I study.
将可携带多种药物、蛋白质和核酸（如DNA和小干扰RNA（siRNA））的可靶向合成载体递送至哺乳动物细胞，作为一种潜在的治疗系统很重要，因为它可避免与病毒相关的问题。
已合成了所谓的多功能纳米载体，其具备多种功能，如靶向性、免受免疫系统影响和调理作用，并且能够将有效载荷递送至核膜。为提高转染效率，已在载体表面连接了一组新型肽，这将增强内体逃逸并促进核进入。用配体靶向原肌球蛋白受体激酶B（TrkB）可增强螺旋神经节细胞培养中的摄取。治疗载荷包括生长因子，如Math-1基因、短发夹RNA和类固醇。与病毒载体相比，当前合成纳米载体存在选择性、内化和转染率较差的问题。
几年内，当合成载体得到优化后，首批基于人用药物/蛋白质/基因产物的疗法将在I期研究中可用。
