Nanoparticle mediated alteration of EMT dynamics: an approach to modulate cancer therapeutics

Abstract

Metastasis is the cause of approximately 90% of cancer-related morbidities and mortalities, which is ascribed to the phenomenon of EMT (epithelial to mesenchymal transition). The pathological activation of EMT during tumour development results in the augmentation of metastasis and invasiveness of the primary tumours. Following EMT, the cells lose their epithelial characteristics and acquire a mesenchymal phenotype. This process involves the disruption of cell–cell and cell–matrix adhesion, changes in cellular polarity and remodelling of cytoskeleton, which are attributed to the enhanced pathogenesis in the tumours. EMT elicits various phenomena such as immune modulation, tumour immune escape, drug resistance and chemoresistance and is also responsible for poor prognosis in cancer. The use of nanoparticles as drug delivery vehicles or as cancer-inhibiting agents has been a topic of extensive research in today's world. Nanoparticles are used as efficient drug-delivering agents owing to their extremely small size and numerous merits such as biocompatibility, biodegradability, non-toxicity, ease of functionalization and encapsulation and enhanced permeability and retention (EPR) effect. Besides, nanoparticles can be modulated to be tumour specific by both passive and active targeting strategies and enhance the intracellular drug concentration in tumours while avoiding toxicity in healthy cells. Thus, the establishment and formulation of a novel nanomedicine might have remarkable and valuable contribution through specific or selective delivery of chemotherapeutic agents and/or inhibitors against EMT related pathways. Additionally, the utilization of their intrinsic cytotoxic activity or their use in the context of precision medicine can be allowed to modulate EMT by targeting the tumour microenvironment. This review deals with the various types of nanomaterials used to inhibit the phenomenon of EMT for achieving a successful anti-metastatic therapeutic regime.