Biodegradable Nanoscale Coordination Polymers for Targeted Tumor Combination Therapy with Oxidative Stress Amplification
Jingjing Liu,1 Min Wu,1 Yutong Pan,1 Yukun Duan,1 Ziliang Dong,2 Yu Chao,2 Zhuang Liu1,* and Bin Liu1,*
1Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore 117585, Singapore
2Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University Suzhou, Jiangsu 215123, China
Nowadays various inorganic nanoparticles that generate highly reactive hydroxyl radical (.OH) on the basis of Fenton-like catalytic activity of metal ions have been designed for chemodynamic therapy. However, the high level of adaptive antioxidants [glutathione (GSH)] in cancer cells could effectively consume .OH to compromise the treatment efficiency and biosafety of these inorganic nanoparticles, and this is a general concern in chemodynamic therapy. Herein, a new biodegradable nanoscale coordination polymer (NCP) is developed by integration of cisplatin prodrug (DSCP) and iron (III) ions through a reverse microemulsion method. The DSCP in the NCPs could react with GSH to release free cisplatin, while the iron (III) ions could be reduced by GSH into iron (II) to enable Fenton reaction, subsequently leading to amplified intracellular oxidative stress. After surface modification of polyethylene glycol (PEG) and cyclo[Arg-Gly-Asp-D-Phe-Lys(mpa)] peptide (cRGD), Fe-DSCP-PEG-cRGD shows an excellent targeting effect against αvβ3-integrin overexpressed tumor cells. Furthermore, Fe-DSCP-PEG-cRGD enables significant chemo and chemodynamic therapy with dramatically enhanced therapeutic efficiency in comparison to relative monotherapies. Importantly, Fe-DSCP-PEG-cRGD could be efficiently cleared out from mice through feces and urine postinjection 7 days. The NCP presented in this work is simple and economical, which shows great biodegradability and biosafety for potential clinical translation.