Benns J M, Kim S W
Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City 84112, USA.
J Drug Target. 2000;8(1):1-12. doi: 10.3109/10611860009009205.
Advancing biotechnology spurs the development of new pharmaceutically engineered gene delivery vehicles with the capability to target specific cell types. The low density lipoprotein (LDL) element of the terplex gene carrier is shown to be efficient in delivery to smooth muscle cells as well as inducing minimal toxicity to A7R5 cells in culture. The terplex system condensed plasmid DNA into polyplex sizes ranging from 100 to 400 nm. Terplex demonstrated higher transfection efficacy than Lipofectin. Lactose was conjugated through a poly(ethyl glycol) (PEG) spacer to poly(L-lysine) (PLL) to tailor a gene carrier capable of condensing plasmid DNA. This cationic polymer targeted Hep G2 cells preferentially in culture. The inclusion of a lactose targeting moiety greatly increased the efficacy of the gene carrier over PEG-PLL and Lipofectin. A biodegradable nanoparticle gene carrier, polysaccharide-graft-PLL and poly(D,L-lactic acid), was synthesized and characterized. The nanoparticle size was controllable by changing the copolymer concentration, where the particles could be as small as 60 nm. When polysaccharide was used in the copolymer, the nanoparticle became more DNA adsorbent. The JLI mAb was linked to PLL. This gene carrier targets the antigen confined to stage II immature cortical thymocytes for leukemia therapy. A 20,000 mw PLL backbone was sufficient for compaction of DNA. Folic acid linked to PLL through a PEG spacer is currently being studied for DNA condensation and delivery to membrane associated folate binding protein positive endothelial cancer cells.
不断发展的生物技术推动了新型药物工程基因递送载体的开发，这些载体能够靶向特定细胞类型。三联体基因载体中的低密度脂蛋白（LDL）成分在递送至平滑肌细胞以及对培养中的A7R5细胞诱导最小毒性方面表现出高效性。三联体系统将质粒DNA浓缩成大小在100至400纳米范围内的多聚体。三联体显示出比脂质体更高的转染效率。乳糖通过聚乙二醇（PEG）间隔物与聚-L-赖氨酸（PLL）偶联，以定制一种能够浓缩质粒DNA的基因载体。这种阳离子聚合物在培养中优先靶向Hep G2细胞。包含乳糖靶向部分大大提高了基因载体相对于PEG-PLL和脂质体的效率。合成并表征了一种可生物降解的纳米颗粒基因载体，即多糖接枝PLL和聚（D，L-乳酸）。通过改变共聚物浓度可控制纳米颗粒大小，颗粒可小至60纳米。当在共聚物中使用多糖时，纳米颗粒对DNA的吸附性更强。JLI单克隆抗体与PLL相连。这种基因载体靶向局限于II期未成熟皮质胸腺细胞的抗原用于白血病治疗。20,000分子量的PLL主链足以压实DNA。目前正在研究通过PEG间隔物与PLL相连的叶酸用于DNA浓缩并递送至与膜相关的叶酸结合蛋白阳性的内皮癌细胞。
