PAMAM dendrimers surface potential

Interest in dendritic polymers (dendrimers) has grown steadily over the past decade due to use of these molecules in numerous industrial and biomedical applications. One particular class of dendrimers, Starburst polyamidoamine (PAMAM) polymers, a new class of nanoscopic, spherical polymers that appears safe and nonimmunogenic for potential use in a variety of therapeutic applications for human diseases. This chapter will focus on investigations into PAMAM dendrimers for in vitro and in vivo nonviral gene delivery as these studies have progressed from initial discoveries to recent animal trials. In addition, we will review other applications of dendrimers where the polymers are surface modified. This allows the opportunity to target-deliver therapeutics or act as competitive inhibitors of viral or toxin attachment to cells. 

The concept of a photo-release and report system has been realized with the 9-(2-methyl-l,3-dithien-2-yl)-9//-thioxanthen-9-ol tethered to a PAMAM dendrimer. Irradiation of the dendrimer system with a U-360 broadband filter results in cleavage of the dithienyl unit to generate, after hydrogen radical transfer, 2-methyl-l,3-dithiane and the tethered thioxanthone 630. The increased fluorescence of the latter confirms the successful photo cleavage. The system offers potential for the generation of high local concentrations of substituted dithianes in the vicinity of the dendrimer surface (Equation 209) <2005JA12458>. 

A common choice of crosslinker for this type of reaction is sulfo-SMCC, which has been used extensively for antibody conjugation (Chapter 20, Section 1.1). A better option for dendrimer conjugation is to use a similar crosslinker design, but one that contains a hydrophilic PEG spacer arm to promote dendrimer hydrophilicity after modification. Derivatization of an amine-dendrimer with a NHS-PEG-maleimide can create an intermediate that is coated with water-soluble PEG spacers. This modification helps to mask any potential for nonspecific interactions that the PAMAM surface may have, while providing terminal thiol-reactive maleimides for coupling ligands (Figure 7.10). 

---