Improving Bioavailability of Hydrophobic Prodrugs through Supramolecular Nanocarriers Based on Recombinant Proteins for Osteosarcoma Treatment
Shidong Wang, Bo Li, Hongliang Zhang, Jiayin Chen, Xin Sun, Jie Xu, Tingting Ren, Yuanyuan Zhang, Chao Ma, Wei Guo, Kai Liu
Abstract
Supramolecular nanodrug assembly driven by supramolecular chemistry is becoming a powerful strategy for medication. The potential of engineered proteins as building blocks for nanoformulations is rarely investigated. Here, we developed a new generation of recombinant protein-based nanodrug carriers, which is very efficient for loading and delivering the hydrophobic prodrug aldoxorubicin. Significantly enhanced anti-tumor effects in osteosarcoma (OS) models were observed. The half-life of the nanodrug reached almost two days and the corresponding bioavailability increased by 17-fold. This is significantly superior to other drug counterparts, empowering long-acting OS treatment scenarios. Importantly, off-target side effects of the prodrug, including cardiotoxicity and lung-metastasis, were greatly mitigated with our medication. Thus, our assembly strategy enables the customized design of advanced nanodelivery systems employing broader biomaterial building blocks for cancer therapy.