New low molecular weight polycation-based nanoparticles for effective codelivery of pDNA and drug.
New low molecular weight polycation-based nanoparticles for effective codelivery of pDNA and drug.
复制标题
DOI：
10.1021/am5046179
复制
发表时间：
2014-10
影响因子：
9.5
通讯作者：
Yu Zhao;Bingran Yu;Hao Hu;Yang Hu;N. Zhao;F. Xu
中科院分区：
文献类型：
--
作者：
Yu Zhao;Bingran Yu;Hao Hu;Yang Hu;N. Zhao;F. Xu
安全有效的新型阳离子纳米粒子在生物医学领域的应用已经引起了广泛的关注。低分子量聚阳离子通常表现出低毒性;然而，它们在药物递送系统中的低效率阻碍了它们的应用。在这项工作中，一系列新的低分子量的2，6-双（1-甲基苯并咪唑基）吡啶（BIP）封端的乙醇胺官能化的聚（甲基丙烯酸缩水甘油酯）（BIP-PGEAs）容易地制造有效的基因和药物的共递送。BIP-PGEAs可以在水溶液中形成定义明确的阳离子纳米颗粒（NPs）。它们可以有效地结合pDNA，具有适当的颗粒大小和介电电位。更重要的是，BIP-PGEA NP的转染效率比线性PGEA（L-PGEA）和传统的“金标准”支化聚乙烯亚胺（25 kDa）高得多。此外，BIP-PGEA NPs可以有效地包埋疏水性抗癌药物，如10-羟基喜树碱（CPT）。通过使用自杀基因治疗系统（其含有胞嘧啶脱氨酶和5-氟胞嘧啶（CD/5-FC））证明BIP-PGEA-CPT NPs的协同抗肿瘤作用。目前的策略，从低分子量的聚阳离子制备明确的阳离子纳米粒子可以提供一个有趣的方法来生产新的多功能，治疗性纳米粒子。
The development of new cationic nanoparticles that are safe and effective for biomedical applications has attracted considerable attention. Low molecular weight polycations generally exhibit low toxicity; however, their poor efficiency in drug delivery systems hampers their application. In this work, a series of new low molecular weight 2,6-bis(1-methylbenzimidazolyl)pyridinyl (BIP)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s (BIP-PGEAs) were readily fabricated for effective codelivery of a gene and a drug. The BIP-PGEAs could form well-defined cationic nanoparticles (NPs) in an aqueous solution. They could effectively bind pDNA with an appropriate particle size and ζ-potential. More importantly, the BIP-PGEA NPs demonstrated much higher transfection efficiencies than linear PGEA (L-PGEA) and the traditional "gold-standard" branched polyethylenimine (25 kDa). Moreover, the BIP-PGEA NPs could effectively entrap a hydrophobic anticancer drug such as 10-hydroxy camptothecin (CPT). The synergistic antitumor effect of the BIP-PGEA-CPT NPs was demonstrated by employing a suicide gene therapy system, which contained cytosine deaminase and 5-fluorocytosine (CD/5-FC). The present strategy for preparing well-defined cationic nanoparticles from low-molecular-weight polycations could provide an intriguing method to produce new multifunctional, therapeutic NPs.