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首页> 外文会议>World biomaterials congress >Glyco-nanoparticles toward nanobiological applications: Synthesis and controlled self-assembly of poly-/oligosaccharide containing block copolymers
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Glyco-nanoparticles toward nanobiological applications: Synthesis and controlled self-assembly of poly-/oligosaccharide containing block copolymers

机译：糖纳米粒子在纳米生物学中的应用：含聚/低聚糖的嵌段共聚物的合成和可控的自组装

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Introduction: Self-assembly of amphiphilic block copolymers (BCPs) that consist of biomacromolecules as one of their building blocks has attracted growing interest in nanobiological applications. Poly-/oligosaccharides are one of the most abundant biomacromolecules which can be obtained from biomass. Thus, our research group has reported various oligosaccharide containing BCPs and their self-assembly in solution and film states. In this presentation, we focus on controlled self-assembly of the oligosaccharide containing BCPs into glyco-nanoparticles in aqueous media for therapeutic molecular delivery application. Materials and Methods: The oligosaccharide containing BCPs were synthesized through copper-catalyzed azide-alkyne cycloaddition of propargyl-functionalized oligosaccharides (maltoheptaose (MH), xyloglucan oligosaccharides (XGO), and beta-cyclodextrin (CD)) with azido end-functionalized polymers (PS, PMMA, PCL and PNIPAM). Self-assembly of the oligosaccharide containing BCPs were performed mainly by nanoprecipitation and thermal aggregation methods. The details were reported in our related publications. Results: The oligosaccharide containing BCPs such as MH-b-PS and MH-b-PMMA were self-assembled into micellar nanoparticles that consist of hydrophilic oligosaccharide shells and hydrophobic polymer cores in aqueous media. The BCPs composed of oligosaccharides and PNIPAM were self-assembled into micellar and vesicular nanoparticles in water by slowly increasing the temperature above the lower critical solution temperature (LCST) of the PNIPAM block. Hydrophobic active guest molecules such as dyes, drugs, and gold nanoparticles were successfully encapsulated into those nanoparticles through self-assembly process. These results were demonstrated by light scattering and imaging techniques including transmission electron microscopy. Discussion: Oligosaccharide containing amphiphilic BCPs can self-assemble into nanoparticles that consist of shells of hydrophilic oligosaccharides and cores of hydrophobic polymers in aqueous media due to energetic repulsion effects between the hydrophobic polymers and water. The hydrophobic guest molecules can be stabilized in the hydrophobic core of the nanoparticles due to hydrophobic effect. Thermo-responsive solubility variation (from hydrophilic to hydrophobic) of the PNIPAM blocks about the LCST induced the self-assembly of the BCPs such as MH-b-PNIPAM. The hydrodynamic radii of those nanoparticles were controlled from tens to hundreds nanometers by this means. Conclusion: The glyco-nanoparticles that can encapsulate active guest molecules were successfully prepared by controlled self-assembly of the oligosaccharide-containing BCPs. The radii of these glyco-nanoparticles were controlled within the size necessary for targeting tumor cells (10-200 nm) by enhanced permeability and retention (EPR) effect. The thermo-responsive formation and dissolution of the glyco-nanoparticles is very important and significant for controlled therapeutic molecular delivery.
机译：简介：两性嵌段共聚物（BCP）的自组装是生物大分子的组成部分之一，在纳米生物学应用中引起了越来越多的兴趣。多糖/寡糖是可从生物质获得的最丰富的生物大分子之一。因此，我们的研究小组报告了各种含寡糖的BCP及其在溶液和薄膜状态下的自组装。在此演示文稿中，我们专注于在水性介质中将含寡糖的BCP进入糖纳米颗粒的受控自组装，以用于治疗性分子递送应用。材料和方法：通过铜催化的叠氮基炔烃环加成炔丙基官能化的寡糖（麦芽七糖（MH），木葡聚糖低聚糖（XGO）和β-环糊精（CD））与叠氮基末端官能化聚合物（BCPs）合成。 PS，PMMA，PCL和PNIPAM）。含寡糖的BCP的自组装主要通过纳米沉淀法和热聚集法进行。有关细节已在我们的相关出版物中报告。结果：含有低聚糖的BCP（例如MH-b-PS和MH-b-PMMA）被自组装成胶束纳米颗粒，该纳米颗粒由亲水性寡糖壳和疏水性聚合物核在水性介质中组成。通过将温度缓慢升高至PNIPAM嵌段的较低临界溶液温度（LCST）以上，由寡糖和PNIPAM组成的BCP可以自组装为水中的胶束和水泡纳米颗粒。疏水活性客体分子（例如染料，药物和金纳米颗粒）通过自组装过程成功地封装到这些纳米颗粒中。通过光散射和包括透射电子显微镜的成像技术证明了这些结果。讨论：由于疏水性聚合物和水之间的能量排斥作用，含有两亲性BCP的寡糖可以自组装成纳米颗粒，该纳米颗粒由亲水性寡糖的壳和疏水性聚合物的核在水性介质中组成。由于疏水作用，疏水客体分子可以稳定在纳米颗粒的疏水核中。围绕LCST的PNIPAM嵌段的热响应溶解度变化（从亲水性到疏水性）引起了MH-b-PNIPAM等BCP的自组装。通过这种方式，将那些纳米颗粒的流体力学半径控制在数十至数百纳米之间。结论：通过控制含寡糖的BCP的自组装，成功制备了可包裹活性客体分子的糖纳米颗粒。这些糖纳米颗粒的半径通过增强的通透性和保留（EPR）效应控制在靶向肿瘤细胞所需的尺寸（10-200 nm）内。糖纳米颗粒的热响应形成和溶解对于控制治疗性分子的传递是非常重要和重要的。

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