Polycationic peptide guided spherical ordered self-assembly of biomacromolecules.
Polycationic peptide guided spherical ordered self-assembly of biomacromolecules.
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DOI：
10.1016/j.biomaterials.2012.08.037
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发表时间：
2012-11
期刊：
影响因子：
14
通讯作者：
K. Shi;F. Cui;Hongshu Bi;Yanbo Jiang;Tao Song
中科院分区：
文献类型：
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作者：
K. Shi;F. Cui;Hongshu Bi;Yanbo Jiang;Tao Song
在不产生新的分子实体或使用载体的情况下实现治疗性生物大分子的长效有效可控递送提供了有希望的替代方案和显著的临床益处。我们发现重组人干扰素-α（rhIFN）可以通过聚阳离子短肽引导的分子自组装形成三维有序结构，其特征在于球形半结晶。构建了自组装相图，确定了成核和有序生长的最佳区域，并对有序自组装体进行了形态、粒径、X射线衍射、圆二色性和生物活性等理化表征。通过改变两种生物大分子的摩尔比，可以在体外和体内调控自组装体的溶解行为。血浆药代动力学表明，s.c.以特定的rhIFN与聚阳离子肽的相对比例施用自组装体提供了长达7天的rhIFN血液水平的显著延长的持续时间。此外，进行分子模拟，以更好地了解它们的结合位点和模式。本文所述的工作证明了生物大分子球形有序自组装用于治疗性蛋白质可控递送应用的可能性。
Achieving effective controllable delivery of therapeutic biomacromolecules for long action without new molecular entities generation or carriers employed offers a promising alternative and significant clinical benefit. We show here that recombinant human interferon-alpha (rhIFN) can form a three dimensional ordered structure that is featured by spherical semi-crystalline through molecular self-assembly directed by a polycationic short peptide. The phase diagrams for self-assembly were constructed to identify the optimal regions for nucleation and ordered growth, and which were followed by the physico-chemical characterization of the ordered self-assemblies, including morphology, particle size, X-ray diffraction, circular dichroism and biological potency evaluations. With varied molar ratio of the two composed biomacromolecules, the dissolution behaviors of the self-assemblies could be manipulated in vitro and in vivo. The plasma pharmacokinetics suggested that s.c. administration of self-assemblies at the specified relative proportion of rhIFN to polycationic peptide offered a significant prolonged duration time of rhIFN blood levels up to seven days. Moreover, molecular simulation was performed to better understand their binding site and mode. The work described here demonstrates the possibility of spherical ordered self-assembly of biomacromolecules for controllable delivery application of therapeutic proteins.