生物小分子的自组装用于仿生光合成和光动力抗肿瘤治疗

发布时间：2018-09-03 11:59

【摘要】：生物小分子能通过分级自组织构筑具有复杂结构的生物功能体系。受生物组装体的启发,生物小分子的分级自组装为构建功能材料提供了一种新策略,也为理解生命现象提供了一个新视角。自然光合成系统能将太阳能高效转化为化学能,为人工太阳能的利用提供了一个蓝本。如何模拟光合成系统中蛋白质、色素分子和辅因子的精巧组织原则,来增强光捕获、电荷分离和催化反应的持续性,成为构建仿生光合体系中的关键科学问题。我们以氨基酸、寡肽、卟啉生物小分子为原料,通过分子自组装构建了一系列仿生光合体系,模拟了光合成系统的组织原则和作用机制。在卟啉基仿生光合体系构建中,采用了两种基本策略,一种为寡肽和卟啉协同共组装,另一种为寡肽或氨基酸-金属离子自组装模板调控卟啉组装。在原始光合体系构建中,使用了热能驱动非光合成的氨基酸-金属离子组装体向前生物色素(原初捕光单元)转化。具体研究内容主要分为以下四个部分:(1)亲水性的二肽通过静电和氢键作用调控卟啉分子的分级自组装,形成了长程有序纤维束。其中卟啉分子以J-聚集组织,且J-聚集体纳米棒定向排布。这模拟了绿色体中菌绿素的组织模式,增强了光吸收和能量传递能力。在耦合了原位矿化的反应中心后,杂化纤维束能实现可见光催化产氢。(2)经左旋多巴分子化学修饰后,两亲性的氨基酸自组装纳米纤维,可以形成含有酚和醌基团的粘附性纳米纤维模板。其可通过配位和静电作用调控金属卟啉分子和金属氧化物(产氧催化剂)的组织。金属卟啉在纳米纤维模表面呈环形排布,醌基团能作为电子受体,这分别模拟了紫色细菌的捕光单元和产氧光合成系统的醌型反应中心,增强了电荷分离。杂化纳米纤维能实现可见光催化产氧。(3)受胱氨酸结石病理过程的启发,以金属离子通过配位和氢键作用调控了胱氨酸结晶的过程,形成了分级有序微球结构,它由纳米棒劈裂生长构成。微球能在晶体生长的过程中通过静电作用封装卟啉和酶分子。微球同时模拟了叶绿体的基粒结构和光-暗偶联反应,增强了光催化燃料生产的可持续性。(4)以氨基酸和金属离子为前生物模型分子,探究了其在水热环境中的进化过程。胱氨酸-锌组装体在水热条件下转化为分级组织的碳掺杂的硫化锌微球,其能同时捕获紫外光和可见光,并能催化原始的光合成反应。这提供了一个原始光合成系统的进化模型,实验上验证了前生物分子在热能和光能的驱动下连续地自进化。生物小分子自组装也能用于生物医药领域。针对光动力治疗中光敏剂药物生物利用度低的问题,利用寡肽调控卟啉分子自组装构建了新型光敏剂给药系统。选用两亲性寡肽的分子调控了与卟啉的静电、疏水和π-π堆叠作用,使光敏剂药物的自组装限制在纳米尺度范围内,形成了纳米球。组装的光敏剂药物纳米球具有许多治疗优势,包括载药量高,响应性释放,肿瘤靶向性。这些特点提高了光敏剂药物的生物利用度,在光动力抗肿瘤治疗中取得了良好效果。以上工作主要利用生物小分子分级自组装,构建了复杂结构的功能体系,用于仿生光合成和抗肿瘤光动力治疗。组装引起功能增强的关键是设计组装基元的分子结构,通过分子间弱相互作用的协同,调节分子、纳米和微米尺度上的自组装过程,控制组装体尺度和结构。
[Abstract]:Biomolecule can construct complex biological function system by self-organization. Inspired by bio-assembly, hierarchical self-assembly of bio-molecule provides a new strategy for constructing functional materials and a new perspective for understanding life phenomena. Natural photosynthesis system can convert solar energy into chemistry efficiently. How to simulate the delicate organization principles of proteins, pigment molecules and cofactors in photosynthetic systems to enhance the sustainability of light capture, charge separation and catalytic reactions has become a key scientific issue in constructing biomimetic photosynthetic systems. A series of biomimetic photosynthetic systems were constructed by molecular self-assembling, which simulated the organization principle and mechanism of the photosynthetic system. In the construction of porphyrin-based biomimetic photosynthetic system, two basic strategies were adopted, one was the co-assembly of oligopeptides and porphyrins, the other was the self-assembly template regulation of oligopeptides or amino acid-metal ions. Porphyrin assembly. In the construction of the original photosynthetic system, non-photosynthesized amino acid-metal ion assemblies were driven by thermal energy to convert into probiotic pigments (original light trapping units). The specific research contents are mainly divided into the following four parts: (1) hydrophilic dipeptides regulate the graded self-assembly of porphyrin molecules through electrostatic and hydrogen bonding interactions, forming a hydrophilic dipeptide. Long-range ordered fiber bundles, in which porphyrin molecules are J-aggregated and J-aggregated nanorods are directionally arranged, simulate the structure pattern of bacteriorubin in green bodies and enhance the ability of light absorption and energy transfer. After modification, amphiphilic amino acid self-assembled nanofibers can form adhesive nanofibers templates containing phenol and quinone groups, which can regulate the structure of metalloporphyrin molecules and metal oxides (oxygen-producing catalysts) by coordination and electrostatic interaction. Metalloporphyrins are annular arranged on the surface of nanofibers, and quinone groups can act as electrons. Receptors, which mimic the light-harvesting units of purple bacteria and the quinone-type reaction centers of oxygen-producing photosynthetic systems, enhance charge separation. Hybrid nanofibers can produce visible-light photocatalytic oxygen. (3) Inspired by the pathological process of cystine stones, metal ions regulate the crystallization of cystine through coordination and hydrogen bonding, forming cystine. The microspheres can encapsulate porphyrins and enzymes by electrostatic interaction during crystal growth. The microspheres also simulate the matrix structure of chloroplasts and the light-dark coupling reaction, which enhances the sustainability of photocatalytic fuel production. (4) Amino acids and metal ions as the pre-biological model. Cystine-zinc assemblies can be transformed into carbon-doped zinc sulfide microspheres with hierarchical structure under hydrothermal conditions. Cystine-zinc assemblies can capture both ultraviolet and visible light and catalyze the original photosynthetic reactions. This provides an evolutionary model of the original photosynthetic system and is verified experimentally. Bio-small molecule self-assembly can also be used in the field of biomedicine. To solve the problem of low bioavailability of photosensitizers in photodynamic therapy, a novel photosensitizer delivery system was constructed by using oligopeptides to regulate porphyrin molecular self-assembly. The electrostatic, hydrophobic and pi-pi stacking with porphyrins restricts the self-assembly of photosensitizer drugs to nano-scale, forming nanospheres. The assembled photosensitizer drug nanospheres have many therapeutic advantages, including high drug loading, responsive release, and tumor targeting. These characteristics improve the bioavailability of photosensitizer drugs, and in light. In this work, we have constructed a functional system of complex structures for biomimetic photosynthesis and anti-tumor photodynamic therapy by using hierarchical self-assembly of small biological molecules. Adjusting molecules, self assembling processes at nanometer and micron scale control the scale and structure of the assembly.
【学位授予单位】：中国科学院大学(中国科学院过程工程研究所)
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R73-36

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