Doxorubicin-loaded dextran-modified GoldMag nanoparticles for targeting hepatocellular carcinoma

Doxorubicin (Dox) is one of the most widely used chemotherapeutic agents for many types of cancer, including hepatocellular carcinoma. However, clinical applications of Dox are limited due to its non-selective cytotoxicity that results in severe adverse effects. To tackle this problem targeted delivery of Dox exclusively to tumour milieu has become clinically prioritised. In this study, we first synthesized and validated Dextran coated GoldMag Nanoparticles (DGMNs) as a potential delivery vehicle for Dox. We then evaluated the cytotoxicity of Dox-DGMNs, the drug and carrier composites, under guidance of external magnetic field (EMF) in hepatocellular carcinoma cell lines and in tumour grafts. Intriguingly, DGMNs exhibited the capacity to prolong Dox release in vitro; hence, Dox-DGMNs significantly enhanced the therapeutic efficiency of the drug in vitro and in vivo, especially under EMF. However, DGMNs were able to significantly decrease systemic adverse effects and inhibit tumour growth compared to the intravenous application of free Dox. Molecular analysis revealed that tumour cells were more affected by Dox-DGMNs with EMF than Dox-DGMNs or Dox alone in terms of apoptosis and DNA damage marker expression. Overall, DGMNs exhibited a substantial potential to serve as a promising drug delivery carrier for magnetically targeted cancer therapy.