Design of "smart" polymers that can direct intracellular drug delivery

One of the important characteristics of biological systems is their ability to change important properties in response to small environmental signals. The molecular mechanisms that biological molecules utilize to sense and respond provide interesting models for the development of "smart" polymeric biomaterials with biomimetic properties. An important example of this is the protein coat of viruses, which contains peptide units that facilitate the trafficking of the virus into the cell via endocytosis, followed by delivery of the genetic material out of the endosome into the cytoplasm, and from there into the nucleus. We have designed several new types of synthetic polymers to facilitate intracellular trafficking of drugs. One of these has been designed to mimic the specific peptides on viral coats that facilitate endosomal escape. Another has been designed to contain pH-degradable bonds, facilitating endosomal escape of the drug only after the bonds are degraded at the acidic pHs of the endosomes. Both types of polymer are responsive to the lowered pH within endosomes, leading to disruption of the endosomal membrane and release of important biomolecular drugs such as DNA, RNA, peptides and proteins to the cytoplasm before they are trafficked to lysosomes and degraded by lysosomal enzymes. In this article, we review our work on the design, synthesis and action of such smart, pH-sensitive polymers. Copyright (C) 2003 John Wiley Sons, Ltd.