Synthesis And Self-assembly Of Amphiphilic Dendrimers

Dendrimers are repeatedly branched, roughly spherical large molecules. A dendrimer usually contains a large internal cavity and plenty of surface functional groups. Many drugs can be placed into the cavities within the dendrimer molecules. Also, through the functional groups on the surface, many drug molecules or functional groups can be conjugated onto the dendrimers. The exact molecular weights of dendrimers with uniform pharmacologic properties further make, them ideal as drug delivery carriers. However, the synthesis of dendrimers is usually complicated, requiring tedious experimental steps and purification techniques. In recent years, with the concept of "click chemistry" being proposed, the synthesis of dendrimers, including amphiphilic dendrimers, has entered a new stage. Meanwhile, studies on the self-assembly of amphiphilic dendrimers are important for their applications in drug delivery.This thesis started with a brief introduce of related background knowledge. Then we proposed to facilely synthesize a series of biodegradable jellyfish-like amphiphilic dendrimers with uniform structure and adjustable molecular weights, and further studie their self-assembly behavior. In addition, a type of worm-like amphiphilic dendrimers was designed, synthesized and prepared as monomolecular micelles.In Chapter Ⅱ, a novel class of jellyfish-like amphiphilic dendrimers composed of 7 hydrophilic poly(ethylene glycol) (PEG) arms and 14 hydrophobic polyester dendrons with β-cyclodextrin (β-CD) as the core molecule was synthesized by a facile method. PEGs were first conjugated to all of C-6 positions of native β-CD, affording mPEG-β-CD. Subsequently, employing the asymmetric monomers of 2-methacryloyloxyethyl acrylate (MAEA) and cysteamine (CA), dendritic polyester architectures were constructed based on the remaining 14 secondary hydroxyl groups at C-2 and C-3 positions, resulting in well-defined jellyfish-shaped amphiphilic dendrimers. The molecular structures and physiochemical properties of these dendrimers were characterized by nuclear magnetic resonance (’H-NMR) and gel permeation chromatography (GPC). The nanoparticles self-assembled from these amphiphilic dendrimers were further characterized by Confocal laser scanning microscopy (CLSM), dynamic light scattering (DLS) and transmission electron microscopy (TEM), demonstrating spherically shaped particles with extremely narrow size distribution as well as unique structure.In Chapter Ⅲ, linear polyethyleneimine (LPEI) with narrow PDI was synthesized. After alternative click reactions with MAEA and CA, as well as the reaction with PEG, worm-like amphiphilic dendrimers were successfully obtained. The molecular structures and physiochemical properties of these dendrimers were characterized by 1H-NMR, and the properties of the dendrimers as monomolecular micelles were also characterized by DLS. Furthermore, we loaded doxorubicin in the dendrimers, and conducted preliminary in vitro and in vivo biological studies.