Synthesis and Characterization of Stimuli-Responsive Star-Like Polypept(o)ides: Introducing Biodegradable PeptoStars.
Synthesis and Characterization of Stimuli-Responsive Star-Like Polypept(o)ides: Introducing Biodegradable PeptoStars.
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DOI：
10.1002/mabi.201600514
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发表时间：
2017-02
影响因子：
4.6
通讯作者：
Regina Holm;Benjamin Weber;P. Heller;K. Klinker;Dana Westmeier;D. Docter;R. Stauber;Matthias Barz
中科院分区：
文献类型：
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作者：
Regina Holm;Benjamin Weber;P. Heller;K. Klinker;Dana Westmeier;D. Docter;R. Stauber;Matthias Barz
星形聚合物是核交联聚合物纳米颗粒类中最小的体系之一。本文报道了一种通用的、直接的三臂星形多肽（聚精氨酸-块聚赖氨酸）聚合物的合成方法，这种聚合物被设计成在谷胱甘肽水平升高时稳定或可降解。Polypept(o)ides是最近引入的一类聚合物，结合了多肽类聚arcos的隐身特性和多肽的功能，从而能够完全基于内源性氨基酸合成材料。星形同族共聚物和嵌段共聚物是由相应的n-羧基氢氧化合物（NCAs）通过亲核开环活性聚合合成的，聚合度（Xn = 25,50,100）、类泊松分子量分布和低分散度（Đ = 1.06-1.15）得到的聚合星形共聚物具有精确控制。通过动态光散射（DLS）测定，星形多肽(o)ides的流体动力半径为5 nm （μ2 < 0.05）。而星形多糖和基于含二硫的引发剂的多肽在溶液中是稳定的，在100 × 10-3 m的谷胱甘肽浓度下会发生降解。二硫化物裂解产生相应的聚合物臂，具有类泊松分子量分布和低分散度（Đ = 1.05-1.12）。最初的细胞摄取和毒性研究表明，PeptoStars对HeLa、HEK 293和DC 2.4细胞具有良好的耐受性。
Star-like polymers are one of the smallest systems in the class of core crosslinked polymeric nanoparticles. This article reports on a versatile, straightforward synthesis of three-arm star-like polypept(o)ide (polysarcosine-block-polylysine) polymers, which are designed to be either stable or degradable at elevated levels of glutathione. Polypept(o)ides are a recently introduced class of polymers combining the stealth-like properties of the polypeptoid polysarcosine with the functionality of polypeptides, thus enabling the synthesis of materials completely based on endogenous amino acids. The star-like homo and block copolymers are synthesized by living nucleophilic ring opening polymerization of the corresponding N-carboxyanhydrides (NCAs) yielding polymeric stars with precise control over the degree of polymerization (Xn = 25, 50, 100), Poisson-like molecular weight distributions, and low dispersities (Đ = 1.06-1.15). Star-like polypept(o)ides display a hydrodynamic radius of 5 nm (μ2 < 0.05) as determined by dynamic light scattering (DLS). While star-like polysarcosines and polypept(o)ides based on disulfide containing initiators are stable in solution, degradation occurs at 100 × 10-3 m glutathione concentration. The disulfide cleavage yields the respective polymeric arms, which possess Poisson-like molecular weight distributions and low dispersities (Đ = 1.05-1.12). Initial cellular uptake and toxicity studies reveal that PeptoStars are well tolerated by HeLa, HEK 293, and DC 2.4 cells.