title: Nanotoxicity: An Interplay of Oxidative Stress, Inflammation and Cell Death.
abstract: Nanoparticles are emerging as a useful tool for a wide variety of biomedical, consumer and instrumental applications that include drug delivery systems, biosensors and environmental sensors. In particular, nanoparticles have been shown to offer greater specificity with enhanced bioavailability and less detrimental side effects as compared to the existing conventional therapies in nanomedicine. Hence, bionanotechnology has been receiving immense attention in recent years. However, despite the extensive use of nanoparticles today, there is still a limited understanding of nanoparticle-mediated toxicity. Bothin vivoandin vitrostudies have shown that nanoparticles are closely associated with toxicity by increasing intracellular reactive oxygen species (ROS) levels and/or the levels of pro-inflammatory mediators. The homeostatic redox state of the host becomes disrupted upon ROS induction by nanoparticles. Nanoparticles are also known to up-regulate the transcription of various pro-inflammatory genes, including tumor necrosis factor-α and IL (interleukins)-1, IL-6 and IL-8, by activating nuclear factor-kappa B (NF-κB) signaling. These sequential molecular and cellular events are known to cause oxidative stress, followed by severe cellular genotoxicity and then programmed cell death. However, the exact molecular mechanisms underlying nanotoxicity are not fully understood. This lack of knowledge is a significant impediment in the use of nanoparticlesin vivo. In this review, we will provide an assessment of signaling pathways that are involved in the nanoparticle- induced oxidative stress and propose possible strategies to circumvent nanotoxicity.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore 117 597, Singapore. puja_khanna@u.nus.edu.
authors.forename: Puja
authors.initials: P
authors.lastname: Khanna
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore 117 597, Singapore. cynthiaong@u.nus.edu.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ong
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore 117 597, Singapore. boon_huat_bay@nuhs.edu.sg.
authors.forename: Boon Huat
authors.initials: BH
authors.lastname: Bay
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, 4 Medical Drive, MD10, Singapore 117 597, Singapore. antbgh@nus.edu.sg.
authors.forename: Gyeong Hun
authors.initials: GH
authors.lastname: Baeg
keywords: DNA damage; ROS generation; apoptosis; inflammation; nanoparticles; nanotoxicity; oxidative stress