NiWo4- RGO composite exerts cytotoxic effects on pancreatic carcinoma cells via a cross-talk between reactive oxygen species-independent canonical autophagy of the mitochondria and epithelial-mesenchymal transition

Cancer is a top-ranked cause for death across the globe and may account for more than 25 million new cases and 15 million deaths every year [1]. As of now, it accounts for approximately one-sixth of the global deaths related to non-communicable diseases [2,3]. Pancreatic cancer is one of the leading causes of death (432242 deaths globally in 2018) across certain countries with a poor survival rate [4]. With pancreas as the primary site, 64,050 new cases and 50,550 deaths are projected to occur across the United States in 2023 [5]. Similarly, for the year 2022 the projections for pancreatic cancer across China were 134,374 new cases and 131,203 deaths [6].

In this connection, pancreatic ductal adenocarcinoma is a common gastro-intestinal malignancy that accounts for more than 90–95% of cancers related to the pancreas (exocrine) with a five-year survival of less than 10% [[7], [8], [9]]. PANC-1 was an isolate of human ductal adenocarcinoma of exocrine pancreas which occupied the walls of the duodenum in a 56-year old male. The doubling-time of this cell line is 28 h and produces low volumes of carcinoembryonic antigen. Also, it can bind to extracellular matrix (ECM) proteins like collagen and fibronectin with high invasive properties in vitro [10,11].

Nanomedicine applies materials at the nanoscale of 1–1000 nm for prevention, diagnosis or delivery of drugs for the treatment of several disorders including cancer. They are biocompatible, and are biomimetic with specific targeting efficacy [[12], [13], [14]]. Although at its infancy, there is a strong rise in global demand for nanomedicine of more than 10% every year, relating to an economic push of 30,000 billion USD by the year 2030 in which one-third accounts for cancer nanomedicine [[15], [16], [17]].

Nanocomposites are significant drug-delivery vehicles for numerous biological macromolecules, wherein materials of different phases and dimensions are implanted into several nanocarriers [[18], [19], [20]]. Among such molecules being carried, standard antitumor agents or other biological molecules stay prioritized for carrying via covalent or non-covalent binding [21,22]. NiWO4-RGO have been prepared extensively as composites along with other metals such as silver and their cytotoxic properties on cancer cells have been elucidated [[23], [24], [25], [26]]. Although there are very few reports of preparing NiWO4-RGO composites, there are no reports on anticancer effects of the composite till this date [27].

As there are limited or no reports on cytotoxic properties of this unique composite, we tried to prepare and test the cytotoxic properties of NiWO4-RGO nanocomposite on PANC-1 adenocarcinoma cells. According to the authors, this is the first-ever international report on cytotoxic effects of NiWO4-RGO nanocomposite on any in vitro cancer cell type and elucidation of the mechanisms along with its biocompatibility.

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