Dendrimer immunogenicity

Other types of branched peptide dendrimers, known as multiple antigen peptides (MAPs), have been synthesized to mimic proteins for applications, for instance as synthetic vaccines, serodiagnostics, peptide inhibitors and intracellular delivery vehicles. Since this concept has been recently described in detail elsewhere [11], only the conceptual framework will be briefly presented here. Tam and coworkers have developed a dendritic core based on lysine units for the construction of MAPs [12-15] (Fig. 3). Carrying antigens at their periphery these MAPs have been designed to increase antigenicity and immunogenicity of peptides. 

Recently three murine antisera to PAMAM dendrimers have been generated using dendrimer-protein conjugates as immunogens [9, 10]. The recognition properties of the three sera are exquisitely specific, recognizing unmodified... 

PAMAM dendrimers or modified PAMAM dendrimers (with oxiamine or sulfhydryl surface functionalities) exclusive of one another. These antisera recognize den-drimers in ELISA (enzyme-linked immunosorbent assays), dot blots and Western blots. The immunogenicity of dendrimer-protein conjugates has implications for therapeutic use of dendrimers as vaccines and we anticipate that antidendrimer antibodies will have applications in patterning and assembling nanostructures containing dendrimers. 

Several peptide dendrimers have been reported/ a major application of which is for the preparation of multiple antigen peptides (MAPs). For example, Tam used the poly (lysine) platform to prepare a MAP. These peptides are used to activate the immune system to produce large numbers of antipeptide antibodies, and their use avoids the immunogenicity and the other disadvantages associated with conventional antigenic systems. 

Applications of cationic dendrimers as transport vehicles have been described, with an emphasis on their use as transfection agents for nucleic acids. They can transfect them into a large number of cell lines and primary culture cells.Dendrimers with protonable amine groups can interact with all forms of nucleic acid by electrostatic interactions to form complexes that condense the nucleic acids. Whereas linear polymers often adopt random coil structures, the 3D structure of a dendrimer is characterized by radial symmetry. To solve many cellular obstacles of gene delivery, functionalization and variation of the dendrimer structure is an important tool that can be applied. These systems have shown stability and non-immunogenic properties for their potential use in a high variety of therapeutic applications and have been successfully used as carriers for nucleic acids and drug delivery. ... 

Gnanou, Taton et al. have reported a series of dendrimer-hke PEOs with an increasing structural complexity (Figure 27.7). In this case, the advantages of the dendritic stracture (multivalency and shape persistence) were combined with the specific properties of PEO, namely stealth effect, biocompatibihty, nontoxidty, low immunogenicity, and antigenicity. 

Duncan and Izzo" listed in their seminal review on dendrimer toxicity some general consideration for polymers and dendrimers for in vivo applications "As a general rule, for any polymeric carrier to be suitable for parenteral application it is essential that the carrier is non-toxic and non-immunogenic, and it should preferably be biodegradable. It must display an inherent body distribution that will allow appropriate tissue targeting to the desired site, but... 

Dendrimers in biological systems have significant advantages such as multivalency for tight binding and more efficient interaction, biocompatibility, immunogenicity, biopermeability, etc. Up to now, diverse research studies into dendrimer-based... 

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