Abstract
Objective:
To develop and evaluate a drug delivery system (DDS) capable of targeting cancer cells while at the same time delivering two chemotherapeutic agents to overcome multidrug resistance (MDR).
Methods:
This study developed a DDS composed of heparin (HA)-coated meta-organic framework (MOF) nanoparticles (HM) designed to deliver doxorubicin (Dox) and quercetin (Que). A range of in vitro and in vivo studies were conducted to determine the characteristics of the HM/Dox/Que nanoparticles, their ability to produce cytotoxic effects in Dox-resistant A549/Dox cells and target and treat solid tumours in a mouse xenograft model of human lung carcinoma.
Results:
This study demonstrated that the HM/Dox/Que nanoparticles reduced cell viability, increased apoptosis, arrested cells in the G0/G1 phase of the cell cycle and reversed MDR in A549/Dox cells in vitro when compared with mono-drug delivery. In a mouse xenograft model of human lung carcinoma, the HM/Dox/Que nanoparticles targeted the tumours and reduced tumour growth as determined by tumour volume.
Conclusion:
The use of HM/Dox/Que nanoparticles might be a viable alternative to traditional chemotherapy of lung carcinoma.
Keywords:
Heparin; chemotherapy; doxorubicin; lung carcinoma; meta-organic framework; quercetin.