ROS-responsive supramolecular antimicrobial peptides-based nanoprodrugs for cervical cancer therapy

Although antimicrobial peptides (AMPs) as a promising natural drugs can efficiently inhibit cervical cancer, poor bioavailability, low tumor selectivity, and non-selective toxicity still hinder its further application in vivo. In order to effectively address these challenges, we have developed a reactive oxygen species (ROS)-responsive targeting nanoprodrug designed for selective therapy of cervical cancer. Such nanoprodrugs (CEC-OxbCD) are fabricated by the supramolecular self-assembly of the modified β-cyclodextrin (β-CD) and AMPs. Antimicrobial peptide, CecropinXJ (CEC), is a cationic antibacterial peptide isolated from 3rd instar larvae of Bombyx mori from Xinjiang, China. OxbCD is an oxidation-responsive β-cyclodextrin material. CEC-OxbCD were synthesized using the nanoprecipitation/self-assembly method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behaviour of CEC-OxbCD were characterised. In vitro and in vivo anti-cancer activities were also evaluated. Nanoprodrugs can be effectively disassembled under stimuli of the tumor- endogenous ROS, resulting in a rapid and on-demand release of antimicrobial peptides (AMPs) with a release rate of 90 %. Furthermore, both in vitro and in vivo experimental results demonstrate that our nanoprodrugs exhibit remarkable therapeutic efficacy against cervical cancer. This work not only provides an effective and promising therapeutic strategy for cervical cancer, but also explores a novel application for AMPs.