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

作者：Tan, Guozhu; Wang, Yu; He, Yuejian; Miao, Guifeng; Li, Yang; Wang, Xiaorui^*

来源：Journal of Controlled Release, 2022, 349: 486-501.

DOI：10.1016/j.jconrel.2022.07.016

• Cation-pi interactions
• Drug delivery
• Responsive sensitivity
• Chemotherapy

Cation-pi 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-pi) micelles drug delivery platform is designed and constructed, based on the block copolymers with random cationic-aromatic sequences (amphiphilic cation-pi polymer). Compared to the polymeric micelles formed by conventional amphiphilic block copolymers which are commonly limited to hydrophobic drugs loading, the engineered poly(cation-pi) micelles can serve as a universal nanocarrier for a wide variety of hydrophobic and hydrophilic drugs with pi-structure. It is found that due to the strong cation-pi interactions integrated in the core of poly(cation-pi) micelles, this nanosystem performs improved structural stability and higher drug loading capability. Especially, in the oxidation-responsive poly(cation-pi) 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-pi interaction enhanced H2O2 -sensitivity of poly(cation-pi) 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.

• 单位
  南方医科大学