Dendrimer surface modification using

Hong et al. (2004) also found that modification of PAMAM dendrimers with a short PEG linker arm could act to reduce nonspecificity caused by the amines on the dendrimer-modified surface. An azido-PEGj-aininc spacer was activated with nitrophenyl carbamate to yield an activated intermediate that could be used to modify the amines on the dendrimer (Figure 7.24). Reaction at high molar ratio resulted in about 61 PEG-azido spacers on the dendrimer. Reduction of the azido group to an amine using triphenylphosphine in THF provided the dendrimer-PEG-amine derivative for surface modification. The added presence of the PEG spacer arm reduced... 

PAMAM]. The final step of this functionalization relied on activation and cross-linking of attached dendrimers with a homobifunctional spacer (DSG or PDITC). Alternatively, after attachment of dendrimers to the surface, glutaric anhydride activated with V-h ydrox vsucc i n i m i de can be used. This surface modification yields a thin, chemically reactive polymer film, which is covalently attached to the glass support and can be directly used for the covalent attachment of amino-modified components, such as DNA or peptides (Fig. 14.2b). 

Dendrimers such as poly(amidoamine) (PAMAM) and poly(propylenimine) (PPI) have also been studied for gene delivery in vitro and in vivo due to their high transfection efficiency. However, the toxicity of the dendrimers is of major concern for their medical use. Generally, in vivo toxicity of dendrimers is related to various factors, including their chemical structure, surface charge, generation and the dose of dendrimer used. Surface modification with PEG or replacement with low generation dendrimers have been reported to be able to improve the biocompatibility of these biomaterials. ... 

Treelike molecules are attracting increasing attention because of their unique structure and properties. Since the first report on dendrimers has been given by F. Vogtie and co-workers [1] in 1978, several synthetic pathways to dendrimers have been developed and a number of core molecules and monomers have been used to prepare different dendrimers [2]. The surface of dendrimers can be modified with many organotransition-metal complex fragments. Ferrocenyl-based dendrimers can be used in the chemical modification of electrodes, in the construction of amperometric biosensors or as multi-electron reservoirs [3]. 

A recent publication described preparation of dendrimers from functional aliphatic polyesters that are based on 2,2-bis(hydroxymethyl)propionic acid [249]. A, Al -dicyclohexylcarbodiimide was used as the coupling agent in a double-stage convergent approach that reduced the number of synthetic and Uquid chromatographic steps required in the preparations and purifications. The hydroxyl functional dendrimers were then subjected to a variety of surface modifications by reactions with different acid chlorides [249]. 

Putting these properties together, one possible mode of use of dendrimers is as nanoscale containers hosting drugs or other payload in their center—providing solubilization, improved pharmacokinetics (slow release/clearing), membrane permeability, and so on. They also allow the possibility of targeting and/or responsive behavior by surface modification. 

Aside from encapsulation of proteins, much work has been done on the surface functionalization of microparticles for cellular interaction and proliferative effects. Surface modification of PLGA microspheres with an amine-terminated dendrimer improved long-term proliferation of chondrocytes without observed changes in the cell phenotype, as compared to monolayer culture systems (Thissen et al. 2006). Additionally, surface functionalization ofpolystyrene magnetic microbeads with the DLL4 notch ligand used in coculture has been shown to efficiently generate T cells from mouse bone marrow hematopoietic stem cells (Taqvi et al. 2006). 

---