Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
J Am Chem Soc. 2012 Feb 29;134(8):3647-50. doi: 10.1021/ja211113n. Epub 2012 Feb 13.
The creation of smart, self-assembling materials that undergo morphological transitions in response to specific physiological environments can allow for the enhanced accumulation of imaging or drug delivery agents based on differences in diffusion kinetics. Here, we have developed a series of self-assembling peptide amphiphile molecules that transform either isolated from molecules or spherical micelles into nanofibers when the pH is slightly reduced from 7.4 to 6.6, in isotonic salt solutions that simulate the acidic extracellular microenvironment of malignant tumor tissue. This transition is rapid and reversible, indicating the system is in thermodynamic equilibrium. The self-assembly phase diagrams show a single-molecule-to-nanofiber transition with a highly concentration-dependent transition pH. However, addition of a sterically bulky Gd(DO3A) imaging tag on the exterior periphery shifts this self-assembly to more acidic pH values and also induces a spherical micellar morphology at high pH and concentration ranges. By balancing the attractive hydrophobic and hydrogen-bonding forces, and the repulsive electrostatic and steric forces, the self-assembly morphology and the pH of transition can be systematically shifted by tenths a pH unit.
智能自组装材料的创建可以对特定生理环境做出形态转变，从而可以根据扩散动力学的差异增强成像或药物输送剂的积累。在这里，我们开发了一系列自组装肽两亲分子，在等渗盐溶液中，当 pH 值从 7.4 略微降低到 6.6 时，无论是从分子中还是从球形胶束中分离出来，都会转化为纳米纤维，模拟恶性肿瘤组织的酸性细胞外微环境。这种转变是快速和可逆的，表明该系统处于热力学平衡状态。自组装相图显示出单一分子到纳米纤维的转变，其转变 pH 值高度依赖于浓度。然而，在外部添加一个大体积的 Gd(DO3A)成像标签会将这种自组装转移到更酸性的 pH 值，并在高 pH 值和浓度范围内诱导球形胶束形态。通过平衡吸引力的疏水和氢键以及排斥的静电和空间力，可以将自组装形态和转变 pH 值系统地移动十分之一 pH 单位。
