A biocompatible nanoformulation of curcumin analogue and curd exosomes targeting EphA2 signalling cascade in head and neck cancer

Abstract

Major therapeutic developments have been made in the prevention of head and neck cancer (HNC), and crucial measures have been implemented for the survival of patients. The advent of cancer nano-theranostic as an effective approach targets cancer by allowing drug aggregation at the tumour site, its proper bioaccessibility, and tumour cell death. Curd exosomes are the cellular interactive nanovesicles, considered a convenient conveyance medium for cargoes still unexplored. Curcumin analogue alanine is primarily recognised for its superior radical scavenging activity and anti-mutagen properties compared with curcumin. The current study focussed on the isolation and characterisation of curd exosomes, followed by their interaction with cancer cells to deliver their content conveniently. Herein, we developed a nanoformulation of curd exosomes loaded with curcumin alanine to determine its bioaccessibility and anti-proliferative effect compared with curcumin alanine free drug. In addition, the influence of curcumin alanine and its nanoformulation on cell morphology, nucleus structures, colony formation potential, and tumour cell death was observed. The expression of EphA2 and its associated molecules was determined using western blot and PCR to explore the mechanism at the cellular level. The recent investigation revealed the encapsulation of curcumin analogue alanine in curd exosomes enhanced the bioaccessibility in contrast with curcumin alanine. Then, we focussed on the curcumin alanine effect on HNC cells to monitor morphological alterations, a reduction in cell multiplication, and triggering apoptosis. Particularly, we found considerable suppression of EphA2 influencing mitochondrial dynamics with the strengthening of mitochondrial fusion MFN1 and MFN2, whereas fission-associated protein DRP1 was down-regulated by the treatment of curcumin alanine nanoformulation. Furthermore, curcumin alanine nanoformulation activates the apoptotic marker caspase-7 and suppresses the anti-apoptotic marker Bcl-xL. Hence, these findings have drawn attention to curd exosomes loaded curcumin alanine nanoformulation impairing cell multiplication and mitochondrial fission, leading to apoptotic cell death, as one of the effective approaches for the treatment of HNC.