物理化学学报 >> 2015, Vol. 31 >> Issue (4): 722-728.doi: 10.3866/PKU.WHXB201503031

软物质 上一篇    下一篇

三条两亲性多肽的自组装行为及酸敏特性

梁菊1, 来丹玉1, 吴文澜2, 李国芝1, 李军波1, 方财林1   

  1. 1 河南科技大学化工与制药学院, 河南洛阳471023;
    2 河南科技大学医学院, 河南洛阳471023
  • 收稿日期:2014-10-16 修回日期:2015-03-02 发布日期:2015-04-03
  • 通讯作者: 梁菊 E-mail:liangju@haust.edu.cn
  • 基金资助:

    国家自然科学基金(51403055)资助项目

Self-Assembly and Acid-Responsive Behavior of Three Amphiphilic Peptides

LIANG Ju1, LAI Dan-Yu1, WU Wen-Lan2, LI Guo-Zhi1, LI Jun-Bo1, FANG Cai-Lin1   

  1. 1 Chemical Engineering and Pharmaceutics School, Henan University of Science and Technology, Luoyang 471023, Henan Province, P. R. China;
    2 Medical School, Henan University of Science and Technology, Luoyang 471023, Henan Province, P. R. China
  • Received:2014-10-16 Revised:2015-03-02 Published:2015-04-03
  • Contact: LIANG Ju E-mail:liangju@haust.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (51403055).

摘要:

通过固相合成法制备了三条疏水端不同的两亲性多肽VVVVVVKKGRGDS (AP1)、C12KKGRGDS(AP2)、FAFAFAKKGRGDS (AP3). 自组装行为研究表明, 三条多肽在中性条件下(pH 7.0)均能形成球形纳米胶束, 透射电子显微镜(TEM)检测其粒径为~30 nm, 动态光散射(DLS)测试其粒径分布均一. 当pH下降为5.0时,肽链AP1的胶束结构被破坏, TEM视野中没有发现任何自组装体, 而肽链AP2和AP3的胶束结构在pH 5.0时依然存在, 但AP2的纳米粒子之间明显发生了部分聚集, 表现为团聚样分布, AP3组装体的粒径明显增大, 形貌变得不规则. DLS测试结果显示, 当pH下降到5.0时, 肽链AP1在1-1000 nm范围内没有出现吸收峰, AP2呈多峰分布, AP3呈宽单峰分布. DLS的测试结果很好地印证了TEM的测试结果. 为了探究三条多肽组装性能不同的二级结构因素, 我们对AP1、AP2和AP3进行了圆二色谱(CD)和傅里叶变换红外(FT-IR)光谱测试. 结果表明, 三条多肽在中性条件下二级结构中均存在一定含量的β-折叠, 当pH下降到5.0 时, AP1 结构中的β-折叠成分显著下降, 出现部分无规卷曲. AP2和AP3的β-折叠成分虽有变化, 但其CD主峰依然存在. 以姜黄素作为模型药物, 进一步确认AP1 载药胶束的释药行为也具有优良的酸敏感特性. AP1、AP2 和AP3 在酸性条件下自组装行为的不同, 表明调控两亲性多肽的疏水端组成有可能是调控多肽自组装性能的有效手段. AP1组装体有望成为理想的pH响应性载体材料.

关键词: 自组装, 纳米胶束, 酸敏感材料, 圆二色谱, 傅里叶变换红外光谱, 多肽二级结构

Abstract:

Three amphiphilic peptides containing KKGRGDS as hydrophilic heads and VVVVVV, C12, and FAFAFA as hydrophobic tails (VVVVVVKKGRGDS (AP1), C12KKGRGDS (AP2), FAFAFAKKGRGDS (AP3)) were designed and prepared using the standard solid-phase peptide synthesis (SPPS) technique. Three peptides assembled into spherical micelles under neutral conditions (pH 7.0) with a size of ~30 nm determined by transmission electron microscope (TEM). Dynamic light scattering (DLS) tests showed that their size distributions were uniform and narrow. In dilute hydrochloric acid (pH 5.0), peptide AP1 presented a sharp aciddependent demicellization transition, with no assembled particles found by TEM and no DLS peak in the range 1-1000 nm. However, the micellar structures of the amphiphilic peptides AP2 and AP3 did not disappear at pH 5.0. TEM results showed that AP2 assembly appeared through aggregation and the shape of AP3 micellar particles became non-spherical or irregular. AP2 assembly at pH 5.0 showed a multiple peak distribution and AP3 assembly showed a broad peak distribution in DLS, consistent with the TEM results. The changes in secondary structures of amphiphilic peptides AP1, AP2, and AP3 at pH 7.0 and 5.0 were confirmed by circular dichroism (CD) and Fourier transform infrared (FT-IR) spectroscopy. We then selected curcumin as a model drug to investigate the drug-loading capacity and in vitro release behavior of peptide AP1 micelles. As a result, AP1 is expected to comprise an ideal acid-responsive drug carrier for the intelligent delivery of anticancer drugs. The differences between AP1, AP2, and AP3 assembly behaviors in neutral and acidic conditions provide a novel and effective approach for regulating self-assembly of peptides. AP1 is expected to offer an ideal pH-responsive functional material.

Key words: Self-assembly, Nano-sized micelle, Acid-sensitive material, Circular dichroism, Fourier transform infrared spectroscopy, Secondary structure of peptide

MSC2000: 

  • O648