ABSTRACT
Nonviral polymeric carriers have been recognized as promising systems for targeted delivery of therapeutic nucleic acid. Key features that can improve the bioefciency of polymeric nanosystems include prolonged circulation in the bloodstream without undesired nontarget interactions, passive and active targeting into the disease site, cellular association and internalization into the target cells, and endosomal escape and subsequent intracellular transport. Because of these many different delivery tasks, nanocarriers are required which continuously optimize their various delivery functions in response to the various specic microenvironments. Nanocarriers can be chemically programmed for this purpose (Ganta et al. 2008; Oupicky and Diwadkar 2003; Roy and Gupta 2003; Wagner 2007). Chemical bonds and conformations can be integrated as sensors for environmental triggers which cleave the sensing bonds or alter the sensing conformation. Thus, the properties of the nanosystem should adopt favorably to the new task in the delivery cascade. Until now, various biological triggers have been exploited for tissue targeting and intracellular delivery, including pH (Meyer and Wagner 2006), temperature (Chilkoti et al. 2002; Zintchenko et al. 2006), and redox or special enzymatic microenvironment (Kommareddy and Amiji 2005; Saito et al. 2003). Another possible strategy is to utilize articial physical triggers for targeting delivery of drugs and genes, like ultrasound, magnetic eld, heat, or light (Berg et al. 2007; Duan et al. 2005; Hernot and Klibanov 2008).
