Combinatorial Chemosensitive Nanomedicine Approach for the Treatment of Breast Cancer

Abstract

Breast cancer is the most commonly diagnosed type of cancer and ranks second among cancer that leads to death. From becoming the foremost reason for global concern, this multifactorial disease is being treated by conventional chemotherapies that are associated with severe side effects, with chemoresistance being the ruling reason. Exemestane, an aromatase inhibitor that has been approved by the US FDA for the treatment of breast cancer in post-menopausal women, acts by inhibiting the aromatase enzyme, in turn, inhibiting the production of estrogen. However, the clinical application of exemestane remains limited due to its poor aqueous solubility and low oral bioavailability. Furthermore, the treatment regimen of exemestane often leads to thinning of bone mineral density. Thymoquinone, a natural compound derived from the oil of the seeds of Nigella sativa Linn, possesses the dual property of being a chemosensitizer and chemotherapeutic agent. In addition, it has been found to exhibit potent bone protection properties, as evidenced by several studies. To mitigate the limitations associated with exemestane and to deliver to the cancerous cells overcoming chemoresistance, the present hypothesis has been put forth, wherein a natural chemosensitizer and chemotherapeutic agent thymoquinone will be incorporated into a lipid nanocarrier along with exemestane for combinatorial delivery to cancer cells. Additionally, thymoquinone being bone protecting will help in ousting the untoward effect of exemestane at the same time delivering it to the required malignant cells, safeguarding the healthy cells, reducing the offsite toxicity, and providing potent synergistic action.

Keywords: Breast cancer; chemoresistance; chemosensitizer; combinatorial delivery; exemestane; thymoquinone.