Impact of Cationic Charge Density and PEGylated Poly(amino acid) Tercopolymer Architecture on Their Use as Gene Delivery Vehicles. Part 1: Synthesis, Self-Assembly, and DNA Complexation.
Impact of Cationic Charge Density and PEGylated Poly(amino acid) Tercopolymer Architecture on Their Use as Gene Delivery Vehicles. Part 1: Synthesis, Self-Assembly, and DNA Complexation.
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DOI：
10.1002/mabi.201800108
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发表时间：
2018-06
影响因子：
4.6
通讯作者：
David Ulkoski;C. Scholz
中科院分区：
文献类型：
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作者：
David Ulkoski;C. Scholz
聚乙二醇化的多氨基酸S与其生物靶标的相互作用取决于其化学性质和构筑单元的空间排列。报道了由聚乙二醇、聚乙二醇、聚L-赖氨酸和聚L-亮氨酸组成的ABC嵌段共聚物的合成、自组装和DNA络合。嵌段共聚物是以端氨基聚乙二醇大分子引发剂(聚乙二醇-b-p(L-赖氨酸)x-b-p(L-亮氨酸)y、聚乙二醇-b-p(L-亮氨酸)x-b-p(L-赖氨酸)y和聚乙二醇-b-p(L-赖氨酸)x-co-p(L-亮氨酸)y)为引发剂，通过N-羧酸酐的无金属活性开环聚合而成。自组装纳米粒子的大小取决于形成方法。纳米沉淀法适用于聚赖氨酸-L嵌段被三氟乙酸酯保护的共聚物，有效直径在92~132 nm之间，而直接溶解在蒸馏水中，有效直径在52~173 nm之间。临界胶束浓度(CMC)分析证实了颗粒大小分析，并显示出明显的分子结构影响；当聚(L-亮氨酸)链段形成C-链段和亲水、拆卸驱动的聚(L-赖氨酸)链段较短时，临界胶束浓度(CMC)最低(8微克毫升-1)。通过凝胶运动和RiboGreen分析来评价DNA的络合作用，强烈地依赖于分子的结构。当聚(L-赖氨酸)和聚(L-亮氨酸)形成单独的嵌段而不是它们形成共聚物时，观察到更有效的dna络合。
The interaction of PEGylated poly(amino acid)s with their biological targets depends on their chemical nature and spatial arrangement of their building blocks. The synthesis, self-assembly, and DNA complexation of ABC terblock copolymers consisting of poly(ethylene glycol), (PEG), poly(l-lysine), and poly(l-leucine), are reported. Block copolymers are produced by a metal-free, living ring-opening polymerization of respective amino acid N-carboxyanhydrides using amino-terminated PEG as macroinitiator: (PEG-b-p(l-Lys)x -b-p(l-Leu)y , PEG-b-p(l-Leu)x -b-p(l-Lys)y , and PEG-b-p((l-Lys)x -co-p(l-Leu)y ). Sizes of self-assembled nanoparticles depend on the formation method. The nanoprecipitation method proves useful for copolymers with the poly(l-lysine) block protected as trifluoroacetate, effective diameters range between 92 and 132 nm, while direct dissolution in distilled water is suitable for the deprotected copolymers, yielding effective diameters between 52 and 173 nm. Critical micelle concentration (CMC) analyses corroborate particle size analyses and show a distinct impact of the molecular architecture; the lowest CMC (8 µg mL-1 ) is observed when the poly(l-leucine) segment forms the C-block and the hydrophilic, disassembly driving poly(l-lysine) segment is short. DNA complexation, evaluated by gel motility and RiboGreen analyses, depends strongly on the molecular architecture. A more efficient DNA complexation is observed when poly(l-lysine) and poly(l-leucine) form individual blocks as opposed to them forming a copolymer.