Abstract：
8-Arm star polypep(o)ides comprising cationic polylysine and hydrophilic polysarcosine blocks with a degree of polymerization (DP) of 30 per block are synthesized. Two different block sequences with polylysine as the inner and polysarcosine as the outer block and vice versa are obtained in addition to a statistical copolymer. Analysis of the enzymatic hydrolysis by the proteolytic enzyme trypsin demonstrates a strong dependence on structural arrangements. While polypept(o)ide disintegration is detectible after 24 h by Size Exclusion Chromatography (SEC), significant hydrolysis of the lysine blocks is only monitored after 48 h by fluorescamine labeling of the produced lysine and clearly accelerated in structures with more accessible polylysine blocks. All structures are capable of complexing plasmid DNA and form gene nanomedicines at sizes around or below 200 nm as determined by Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), and Transition Electron Microscopy (TEM). The polyplex formation is slightly enhanced for both block structures over the random copolypept(o)ide. Moreover, it is demonstrated that the polyplexes can transport through mucus. The results highlight the importance of structural control in compartmentalized polymeric gene vector candidates with hydrophilic domains for potential mucosal delivery.
摘要：
合成包含阳离子聚赖氨酸和亲水性聚肌氨酸嵌段的8-臂星形polypepp（o）化物，每个嵌段的聚合度（DP）为30。除了统计共聚物外，还获得了两种不同的嵌段序列，其中聚赖氨酸作为内部嵌段，多肌氨酸作为外部嵌段，反之亦然。蛋白水解酶胰蛋白酶的酶促水解分析证明了对结构排列的强烈依赖性。虽然通过大小排阻色谱法(SEC)在24小时后可检测到polypeppt(o)ide崩解，赖氨酸嵌段的显著水解仅在48小时后通过荧光胺标记产生的赖氨酸进行监测，并且在具有更容易获得的聚赖氨酸嵌段的结构中明显加速。通过动态光散射（DLS）测定，所有结构都能够与质粒DNA复合并形成大小在200nm左右或以下的基因纳米药物。纳米粒子跟踪分析(NTA)和过渡电子显微镜（TEM）。与无规共聚物（o）ide相比，两种嵌段结构的复合物形成均略有增强。此外，证明了聚合复合物可以通过粘液运输。结果强调了结构控制在具有亲水性结构域的隔室化聚合物基因载体候选物中对于潜在的粘膜递送的重要性。
