Bifunctional Therapy by Zinc-Cobalt Bimetal-Organic Framework with Encapsulated Doxorubicin to Overcome Drug-Resistance

Graphical Irresistible : An antineoplastic chemotherapeutic nanoparticle (NP) is constructed based on zinc-cobalt bimetal-organic frameworks encapsulated with doxorubicin (DOX). Therapeutic effects are tested on cancer cell lines and its DOX-resistant counterparts, and cellular characteristics are further examined to demonstrate the effectiveness of NPs in overcoming drug-resistance. Drug resistance is a major challenge in antineoplastic chemotherapy, which could be possibly solved through multifunctional anti-cancer therapy. This study constructs a drug delivery system with Zn(II)-Co(II) bimetal-organic framework nanoparticles with encapsulated doxorubicin (DOX), a model chemotherapeutic molecule. Beyond conventional therapeutic mechanisms powered by DOX, the newly applied Co(II) to the drug delivery system catalyzes the generation of reactive oxygen species (ROS) through a Fenton-like process, leading to necrosis due to oxidative stress beyond threshold. The system displayed DOX-based and Co(II)-based dual mechanism anti-cancer therapy to overcome DOX-resistance while demonstrating significant cytotoxicity promotion in non-resistant cell lines, as effects of ROS were further acknowledged by following cell characteristic examinations. This bifunctional DOX-encapsulated bimetal-organic framework nanoparticle opens a new strategy to construct multiple anti-cancer mechanism drug delivery systems with great simplicity.