Tumour specific targeted in vitro theranostics application of fabricated nanostructures in a multi-drug resistant ovarian carcinoma cell line

Abstract

Ovarian cancer is called the “Silent Killer” as it is often diagnosed in advanced stages of the disease or misdiagnosed which ends with a poor prognostic outcome for the patient. A high rate of disease relapse, a high incidence-to-mortality ratio as well as acquired multidrug resistance makes it necessary to find alternative diagnostic- and therapeutic tools for ovarian cancer. Nanotechnology describes molecular devices with at least one dimension in the sub- 1μm scale and has been suggested as a possible solution for overcoming challenges in cancer multidrug resistance as well as early diagnosis of the disease. One-pot synthesized gold nanoparticles were used to demonstrate in vitro drug delivery of doxorubicin in a manner which overcame the cytoprotective mechanisms of a multidrug resistant ovarian carcinoma cell line (A2780cis) by inducing apoptosis mediated by caspase-3 within 3h of treatment. The gold nanoparticles were further functionalized with nitrilotriacetic acid and displayed specific interaction with a 6xHis-tagged cancer targeting peptide, chlorotoxin. Proprietary indium based quantum dots were functionalized with the same surface chemistry used for gold nanoparticles and bioconjugated with chlorotoxin. Wide field fluorescence studies showed the peptide-quantum dot construct specifically targeted enhanced green fluorescent tagged matrix metalloproteinase-2 transfected A2780cis cells in a specific manner. The cytoprotective multidrug resistant mechanisms of the ovarian carcinoma was overcome successfully with a single dose of doxorubicin loaded gold nanoparticles and tumour specific targeting was demonstrated using quantum dots with a similar surface chemistry used for the gold nanoparticles.