Institute of Organic Chemistry and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Lessingstraße 8, 07743, Jena, Germany.
Institute of Pharmacy, Pharmaceutical Technology and Biopharmacy, Friedrich Schiller University Jena, Lessingstraße 8, 07743, Jena, Germany.
Macromol Rapid Commun. 2020 Mar;41(6):e1900668. doi: 10.1002/marc.201900668. Epub 2020 Feb 19.
A highly efficient transfection agent is reported that is based on terpolymer consisting of N-(2-hydroxypropyl)methacrylamide (HPMA), N-(3-guanidinopropyl) methacrylamide (GPMA), and N-(2-indolethyl)methacrylamide monomers (IEMA) by analogy to the amphipathic cell-penetrating peptides containing tryptophan and arginine residues. The incorporation of the indole-bearing monomer leads to successful plasmid DNA condensation even at a nitrogen-to-phosphate (N/P) ratio of 1. The hydrodynamic diameter of polyplexes is determined to be below 200 nm for all N/P ratios. The transfection studies demonstrate a 200-fold increase of the transgene expression in comparison to P(HPMA-co-GPMA) with the same guanidinium content. This study reveals the strong potential of the indole group as a side-chain pendant group that can increase the cellular uptake of polymers and the transfection efficiency of the respective polyplexes.
据报道，一种基于 N-(2-羟丙基)甲基丙烯酰胺 (HPMA)、N-(3-胍丙基)甲基丙烯酰胺 (GPMA) 和 N-(2-吲哚乙基)甲基丙烯酰胺单体 (IEMA) 的三元共聚物的高效转染试剂，该共聚物类似于含有色氨酸和精氨酸残基的两亲性细胞穿透肽。引入含吲哚的单体可成功实现质粒 DNA 的缩合，即使在氮磷比（N/P）为 1 的情况下也是如此。对于所有 N/P 比，聚电解质复合物的水动力学直径均确定在 200nm 以下。转染研究表明，与具有相同胍含量的 P(HPMA-co-GPMA)相比，转基因表达提高了 200 倍。该研究揭示了吲哚基团作为侧链取代基的强大潜力，它可以增加聚合物的细胞摄取和相应的聚合物复合物的转染效率。
