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Abstract

Self assembly between cations and anions is ubiquitous throughout nature. Important biological structures such as chromatin often use poly­valent assembly between a polycation and a polyanion. The biomedical importance of synthetic polycations arises from their affinity to polyanions such as nucleic acid and heparan sulfate. However, the limited biocompatibility of synthetic polycations hampers the realization of their immense potential. By examining biocompatible cationic peptides, we hypothesize that a biocompatible polycation should be biodegradable and made from endogenous cations. We design an arginine-based biodegradable polycation and demonstrate that it is more compatible by several orders of magnitude than conventional polycations in vitro and in vivo. This biocompatibility diminishes when L-arginine is substituted with D-arginine or when the biodegradable ester linker is changed to a biostable ether linker. We believe that this design can lead to many biocompatible polycations that can significantly advance a wide range of applications including controlled release, tissue engineering, biosensing, and medical devices.