Bioinspired poly(cation-π) micelles drug delivery platform for improving chemotherapy efficacy

Cation-π interactions widely exist in biological systems and play important roles in driving the self-assembly of biological molecules, stabilizing protein structures, and mediating molecular recognitions. Herein, a novel bioinspired poly(cation-π) micelles drug delivery platform is designed and constructed, based on the block copolymers with random cationic-aromatic sequences (amphiphilic cation-π polymer). Compared to the polymeric micelles formed by conventional amphiphilic block copolymers which are commonly limited to hydrophobic drugs loading, the engineered poly(cation-π) micelles can serve as a universal nanocarrier for a wide variety of hydrophobic and hydrophilic drugs with π-structure. It is found that due to the strong cation-π interactions integrated in the core of poly(cation-π) micelles, this nanosystem performs improved structural stability and higher drug loading capability. Especially, in the oxidation-responsive poly(cation-π) micelles as proof-of-concept, the process of stimuli-induced drug release is found significantly accelerated under the biologically relevant level of H2O2 in tumor microenvironment. Furthermore, the mechanism of cation-π interaction enhanced H2O2-sensitivity of poly(cation-π) micelles is proposed, and the improving anti-tumor efficacy is demonstrated in both in vitro and in vivo models. This work broadens the construction strategy of polymeric micelles and offers a universal drug delivery platform for efficient tumor chemotherapy.