Recent advances in the field of nanotechnology have paved the way for novel biomedical applications of nanomaterials. Nanoscale vanadates possess unique properties and have been reported to elicit anti-aging, antibacterial, anti-cancer and antioxidant effects. Likewise, they are potentially applied as bioimaging, drug delivery, theranostic or would healing agents, as well as biosensors. In this review, we highlight and critically discuss biomedical applications of vanadate nanostructures. This review article aims at identifying molecular hallmarks of vanadate nanomaterial-mediated cytotoxicity. Our analysis reveals that depending on size, morphology, composition, concentration, and external conditions (pH, irradiation, etc.) nanoscale vanadates induce oxidative stress, mitochondrial dysfunction, and lysosomal damage, culminating in cell death. Notably, besides apoptosis, nanosized vanadates trigger immunogenic non-apoptotic cell death pathways (ferroptosis and necroptosis) primarily due to overproduction of reactive oxygen species (ROS). Thus, our review demonstrates that nanostructured vanadates are multifaceted pharmacological agents with a wide spectrum of diverse biological applications. Our analysis demonstrates that redox activity of nanostructured vanadates is a key factor determining biological responses to them. Thus, more studies should focus on elucidating the biologically-relevant redox mechanisms of nanosized vanadates.

BIOCEV 1st Faculty of Medicine Charles University Průmyslová 595 Vestec 25250 Czech Republic

Center of Excellence in Polymeric Materials for Medical Practice Devices Department of Chemical Engineering Faculty of Engineering Chulalongkorn University Bangkok 10330 Thailand

Department of Chemical Sciences University of Johannesburg P O Box 17011 Johannesburg Doornfontein 2028 South Africa

Department of Nanostructured Materials Institute for Scintillation Materials of the National Academy of Sciences of Ukraine 60 Nauky ave Kharkiv 61072 Ukraine

Department of Physics and Electronics CHRIST Bengaluru Karnataka 560029 India

Institute of Health National University of Water and Environmental Engineering 11 Soborna st Rivne 33028 Ukraine

International and Inter University Centre for Nanoscience and Nanotechnology School of Energy Materials School of Nanoscience and Nanotechnology and School of Chemical Science Mahatma Gandhi University Kottayam Kerala 686560 India

Rivne Regional Clinical Hospital 78 g Kyivska st Rivne 33007 Ukraine

TrEST Research Park TC 4 2322 GEM Building Opposite College of Engineering Trivandrum Kulathoor Rd Kerala Sreekariyam Trivandrum 695016 India

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