Immunoreactivity changes of human serum albumin and alpha-1-microglobulin induced by their interaction with dendrimers.

Dendrimers are hyperbranched polymers for delivery of therapeutic genetic material to cancer cells. The fine tuning chemical modifications of dendrimers allow for the modification of the composition. The architecture and the properties of dendrimers are key factors to improve their in vitro and in vivo properties such as biocompatibility with cells and tissues and their pharmacokinetic/pharmacodynamic behavior. The side effects of dendrimers on structure and function of proteins is an important question that must be addressed. We herein describe the effect of newly synthesized piperidine-based cationic phosphorous dendrimers of 2 generations and commercial cationic, neutral and anionic poly(amidoamine) (PAMAM) dendrimers of 4th generation on immunochemical properties of 2 serum proteins: human serum albumin (HSA) and alpha-1-microglobulin (A1M). Both can bind and transfer ligands in blood, including hormones, fatty acids, toxins and drugs, and have immunoreactivity properties. Comparing the effects of piperidinium-terminated phosphorus and cationic, neutral and anionic PAMAM dendrimers on HSA and A1M, we conclude that, in the case of equimolar complexes, these dendrimers had no significant effect on immunoreactivity of proteins. In contrast, the formation of complexes in which a protein is fully bound to dendrimers leads to partial (1.2-2.3 times) reduction in protein immunoreactivity. The most important fact is that dendrimer-induced change in immunoreactivity of proteins is not complete, even if the protein is entirely bound by dendrimers. This means that the application of dendrimers in vivo will not totally hamper the immunoreactivity of these proteins and antibodies.