Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany.
Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany.
Macromol Biosci. 2015 Aug;15(8):1159-73. doi: 10.1002/mabi.201500022. Epub 2015 May 13.
Herein we describe the synthesis of poly-L-lysine-b-poly[N-(2-hydroxypropyl)-metha-crylamide)] (poly[HPMA]) block copolymers by combination of solid phase peptide synthesis or polymerization of α-amino acid-N-carboxy-anhydrides (NCA-polymerization) with the reversible addition-fragmentation chain transfer polymerization (RAFT). In the presence of p-DNA, these polymers form polyplex micelles with a size of 100-200 nm in diameter (monitored by SDS-PAGE and FCS). Primary in vitro studies with HEK-293T cells reveal their cellular uptake (FACS studies and CLSM) and proof successful transfection with efficiencies depending on the length of polylysine. Moreover, these polyplexes display minimal toxicity (MTT-assay and FACS-measurements) featuring a p[HPMA] corona for efficient extracellular shielding and the potential ligation with antibodies.
在此，我们描述了通过固相肽合成或 α-氨基酸-N-羧酸酐（NCA 聚合）与可逆加成-断裂链转移聚合（RAFT）的组合来合成聚-L-赖氨酸-b-聚[N-（2-羟丙基）-甲丙烯酰胺]（聚[HPMA]）嵌段共聚物。在 p-DNA 的存在下，这些聚合物在直径为 100-200nm 的范围内形成聚多肽胶束（通过 SDS-PAGE 和 FCS 监测）。与 HEK-293T 细胞的初步体外研究表明，它们具有细胞摄取能力（FACS 研究和 CLSM），并证明了转染效率取决于聚赖氨酸的长度。此外，这些聚多肽具有最小的毒性（MTT 测定和 FACS 测量），其特点是具有有效的细胞外屏蔽作用的 p[HPMA]冠和与抗体的潜在连接。
