Bioresponsive polyplexes - chemically programmed for nucleic acid delivery.

INTRODUCTION: The whole delivery process of nucleic acids is very challenging. Appropriate carrier systems are needed, which show extracellular stability and intracellular disassembly. Viruses have developed various strategies to meet these requirements, as they are optimized by biological evolution to transfer genetic information into host cells. Taking viruses as models, smart synthetic carriers can be designed, mimicking the efficient delivery process of viral infection. These 'synthetic viruses' are pre-programmed and respond to little differences in their microenvironment, caused by either exogenous or endogenous stimuli. AREAS COVERED: This review deals with polymer-based, bioresponsive nanosystems (polyplexes) for the delivery of nucleic acids. Strategies utilizing pH-responsiveness, redox-responsiveness as well as sensitivity towards enzymes will be described more in detail. Systems, which respond to other endogenous triggers (i.e. reactive oxygen species, adenosine triphosphate, hypoxia), will be briefly illustrated. Moreover, some examples for combined bioresponsiveness will be presented. EXPERT OPINION: Bioresponsive polyplexes are a smart way to facilitate programmed, timely delivery of nucleic acids to desired, specific sites. Nevertheless, further optimization is necessary to improve the still moderate transfection efficiency and specificity - also in regard to medical translation. For this purpose, precise carrier structures are desirable and stability issues of bioresponsive systems must be considered.