Polymer genomics: an insight into pharmacology and toxicology of nanomedicines.
Synthetic polymers and nanomaterials display selective phenotypic effects in cells and in the body signal transduction mechanisms involved in inflammation, differentiation, proliferation, and apoptosis. When physically mixed or covalently conjugated with cytotoxic agents, bacterial DNA or antigens, polymers can drastically alter specific genetically controlled responses to these agents. These effects, in part, result from cooperative interactions of polymers and nanomaterials with plasma cell membranes and trafficking of polymers and nanomaterials to intracellular organelles. Cells and whole organism responses to these materials can be phenotype or genotype dependent. In selected cases, polymer agents can bypass limitations to biological responses imposed by the genotype, for example, phenotypic correction of immune response by polyelectrolytes. Overall, these effects are relatively benign as they do not result in cytotoxicity or major toxicities in the body. Collectively, however, these studies support the need for assessing pharmacogenomic effects of polymer materials to maximize clinical outcomes and understand the pharmacological and toxicological effects of polymer formulations of biological agents, i.e. polymer genomics.
Kabanov
Alexander V
AV
Center for Drug Delivery and Nanomedicine and Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Durham Research Center, 985830 Nebraska Medical Center, Omaha, Nebraska 68198-5830, USA. akabanov@unmc.edu
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008566:Membranes / Q000378:metabolism; D053758:Nanoparticles / Q000633:toxicity*; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D011108:Polymers / Q000627:therapeutic use* / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D043922:Toxicogenetics
D011108:Polymers