Grieshaber Sarah E, Paik Bradford A, Bai Shi, Kiick Kristi L, Jia Xinqiao
Department of Materials Science and Engineering, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19716, USA.
Soft Matter. 2013 Feb 7;9(5):1589-1599. doi: 10.1039/C2SM27496E.
Elastin-mimetic hybrid copolymers with an alternating molecular architecture were synthesized the step growth polymerization of azide-functionalized, telechelic poly(-butyl acrylate) (PBA) and an alkyne-terminated, valine and glycine-rich peptide with a sequence of (VPGVG) (VG2). The resultant hybrid copolymer, [PBA-VG2], contains up to six constituent building blocks and has a polydispersity index (PDI) of ~1.9. Trifluoroacetic acid (TFA) treatment of [PBA-VG2] gave rise to an alternating copolymer of poly(acrylic acid) (PAA) and VG2 ([PAA-VG2]). The modular design permits facile adjustment of the copolymer composition by varying the molecular weight of PAA (22 and 63 repeat units). Characterization by dynamic light scattering indicated that the multiblock copolymers formed discrete nanoparticles at room temperature in aqueous solution at pH 3.8, with an average diameter of 250-270 nm and a particle size distribution of 0.34 for multiblock copolymers containing PAA and 0.17 for those containing PAA. Upon increasing the pH to 7.4, both types of particles were able to swell without being disintegrated, reaching an average diameter of 285-300 nm for [PAA-VG2] and 330-350 nm for [PAA-VG2], respectively. The nanoparticles were not dissociated upon the addition of urea, further confirming their unusual stability. The nanoparticles were capable of sequestering a hydrophobic fluorescent dye (pyrene), and the critical aggregation concentration (CAC) was determined to be 1.09 × 10 or 1.05 × 10 mg/mL for [PAA-VG2] and [PAA-VG2], respectively. We suggest that the multiblock copolymers form through collective H-bonding and hydrophobic interactions between the PAA and VG2 peptide units, and that the unusual stability of the multiblock nanoparticles is conferred by the multiblock architecture. These hybrid multiblock copolymers are potentially useful as pH-responsive drug delivery vehicles, with the possibility of drug loading through concerted H-bonds and hydrophobic interactions.
通过叠氮官能化的遥爪聚（丙烯酸丁酯）（PBA）与炔基封端的、富含缬氨酸和甘氨酸且序列为（VPGVG）（VG2）的肽进行逐步生长聚合反应，合成了具有交替分子结构的弹性蛋白模拟杂化共聚物。所得的杂化共聚物[PBA-VG2]包含多达六个组成结构单元，且多分散指数（PDI）约为1.9。用三氟乙酸（TFA）处理[PBA-VG2]得到了聚（丙烯酸）（PAA）和VG2的交替共聚物（[PAA-VG2]）。这种模块化设计允许通过改变PAA的分子量（22和63个重复单元）轻松调整共聚物组成。动态光散射表征表明，在室温下，pH为3.8的水溶液中，多嵌段共聚物形成离散的纳米颗粒，对于含PAA的多嵌段共聚物，平均直径为250 - 270 nm，粒径分布为0.34；对于含PAA的多嵌段共聚物，粒径分布为0.17。将pH提高到7.4时，两种类型的颗粒都能够膨胀而不崩解，[PAA-VG2]的平均直径分别达到285 - 300 nm，[PAA-VG2]的平均直径分别达到330 - 350 nm。添加尿素后纳米颗粒不会解离，进一步证实了它们不同寻常的稳定性。这些纳米颗粒能够螯合一种疏水性荧光染料（芘），对于[PAA-VG2]和[PAA-VG2]，临界聚集浓度（CAC）分别测定为1.09×10或1.05×10 mg/mL。我们认为，多嵌段共聚物是通过PAA和VG2肽单元之间的集体氢键和疏水相互作用形成的，并且多嵌段纳米颗粒不同寻常的稳定性是由多嵌段结构赋予的。这些杂化多嵌段共聚物作为pH响应型药物递送载体具有潜在用途，有可能通过协同氢键和疏水相互作用进行药物负载。
