Gold nanorods decorated with a cancer drug for multimodal imaging and therapy.

Abstract

Cancer, a condition with uncontrolled cell division, is the second leading cause of death worldwide. The currently available techniques for the imaging and treatment of cancer have their own limitations and hence a combination of more than one modality is expected to increase the efficacy of both diagnosis and treatment. In the present study, we have developed a multimodal imaging and therapeutic system by incorporating a chemotherapeutic drug, mitoxantrone (MTX) onto PEG coated gold nanorods (GNR). Strong absorption in the near-infrared (NIR) and visible regions qualifies GNR as an efficient photothermal (PTT) agent upon irradiation with either a NIR or visible laser. Additionally, the enhanced electric field of GNR makes it a suitable substrate for surface enhanced Raman scattering (SERS). Modification of GNR with amino PEG offers biocompatibility without affecting its optical property. In order to achieve tumor specificity, GNR-PEG was conjugated with tumor specific marker that can target cancer cells, leaving the normal cells unaffected. The incorporation of fluorescent chemotherapeutic drug mitoxantrone onto GNR-PEG facilitates chemotherapy as well as fluorescence imaging. The therapeutic efficacy of the developed GNR based system is tracked using fluorescence imaging and Raman imaging. The careful design of the system also facilitates the controlled release of the drug by photothermal triggering. Likewise, the imaging modality could be chosen as either Raman or fluorescence to monitor drug release in accordance with irradiation. The physico-chemical properties, and drug release profiles under different physiological conditions have been well studied. Finally, the developed system was tested for its therapeutic efficacy using cancer cells, in vitro. The receptor mediated cell uptake was more effective in folate receptor over-expressing cancer cells than in the normal and low-expressing cells. Accordingly the percentage of cell death was higher in folate receptor over-expressing cancer cells, which was further enhanced due to the effect of the dual therapeutic approach. The cell uptake and treatment efficacy was monitored using fluorescence microscopy and SERS. In conclusion, the developed GNR-PEG-MTX system is found to be an efficient multimodal therapeutic agent against cancer which could be tracked using two different techniques.