Abstract
Polyion complex (PICs) micelles are formed through the self-assembly of polyelectrolytes bearing opposite charges. The ability to form PICs under fully aqueous conditions makes them attractive for the encapsulation of biopolymers such as proteins and nucleic acids for potential therapeutic applications. Stimuli-responsive PIC micelles have the potential to release their cargo under specific biological conditions. We describe here the development of PIC micelles formed from two self-immolative polymers (SIPs) with complementary charges. The polycationic SIP, having pendent ammonium groups, undergoes depolymerization in response to light. The polyanionic SIP, bearing pendent carboxylates and a stabilizing PEG block, undergoes depolymerization in response to a pH change from 7.4 to 6. SIP PICs composed of a 0.6 anion:cation ratio remain well dispersed at pH 7.4, but degrade at pH 6, primarily due to depolymerization of the anionic block. Irradiation with UV light leads primarily to depolymerization of the cationic block. In vitro cytotoxicity assays with C2C12 cells indicate that the PICs are quite well tolerated by the cells with low cytotoxicity up to about 0.5 mg mL(-1). Overall, these PICs are a new platform that can potentially be used for the encapsulation and stimulus-mediated release of ionic cargo.