Temperature- and pH-responsive smart polymers for gene delivery

Biopolymer therapeutics are likely to be the next generation of medicines, and nucleic acids are among the most important of these potential drugs. The challenges of delivering genes are formidable and advanced biomimetic materials are expected to be required. Polymers that can respond to changes in temperature and pH are good candidates for gene delivery vehicles, as the stimulus response can be used to alter their interactions with the drug payload. In this review, the chemistries underlying these responsive polymers are considered, and the possible mechanisms by which nucleic acids, primarily DNA, can be protected during transit and released at target sites are outlined. Sophisticated multicomponent polymers are being developed, with functionalities designed to overcome the barriers to gene delivery at both the systemic and local level; key examples are highlighted. The extension of these materials to yet more advanced therapies, such as cell delivery and regenerative medicine, is outlined as an emerging technology for the future.