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[1]-[6].
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.
The authors acknowledge financial support from CNRS, the PolyNat Carnot Institute, and Labex ARCANE (ANR-11-LABX-0003-01).
References:
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