Probing and Preventing Quantum Dot-Induced Cytotoxicity with Multimodal α-Lipoic Acid in Multiple Dimensions of The Peripheral Nervous System

Abstract

A long circulating liposomal, nanoscale blood pool agent encapsulating traditional iodinated contrast agent (65 mg I/mL) was used for micro-computed tomography (CT) imaging of rats implanted with R3230AC mammary carcinoma. Three-dimensional vascular architecture of tumors was imaged at 100-micron isotropic resolution. The image data showed good qualitative correlation with pathologic findings. The approach holds promise for studying tumor angiogenesis and for evaluating anti-angiogenesis therapies.

Computed Tomography Imaging of Primary Lung Cancer in Mice Using a Liposomal-Iodinated Contrast Agent

“…While promising, the use of conventional contrast agents present challenges in quantitative perfusion analysis due to rapid leakage into the extravascular space, even during first pass imaging. Furthermore, the molecular nature of iodinated contrast agents, similar in size to Magnetic Resonance (MR) contrast agents, makes them less sensitive to changes in vascular morphology that occur at the nano and micro scales [7], [8], [9]. Macromolecular and nanoparticle-based imaging agents could potentially provide a more accurate measurement of nodule perfusion and vessel permeability.…”

Mechanisms of cellular adaptation to quantum dots – the role of glutathione and transcription factor EB

“…The cadmium center of these complexes can assume several different coordination geometries with the glutathione molecule, rendering glutathione a highly effective cadmium chelator (Singhal et al 1987;Belcastro et al 2009). However, CdTe QD toxicity does not result from the simple addition of cadmium and tellurium components, but rather depends on the unique physicochemical properties of the nanocrystal structure as a sum greater than its parts (Jain et al 2009). Undifferentiated rat pheochromocytoma cells (PC 12) are an attractive model to study the adaptive cellular response to oxidative stress, because they are well characterized and the signal transduction pathways have been previously described in detail (Greene and Tischler 1976;Kaplan 1998;Patapoutian and Reichardt 2001;Vaudry et al 2002).…”

“…Exposure to both artificial and biological NPs can lead to the disruption of cellular redox status and activation of compensatory mechanisms. However, when exposed to toxic nanomaterials for a short time or in low nanomolar concentrations, cells can successfully adapt by engaging antioxidant defenses and lipid re-distribution processes (Jain et al 2009;Khatchadourian and Maysinger 2009). Specific mechanisms that mediate these adaptive cellular processes remain unclear.…”

Epigenetic mechanisms in nanomaterial-induced toxicity

“…In addition, oxidative stress may cause point mutations, DNA adducts, fragmentation of chromosomes promoting DNA damage [53,54] indirectly, by activating intracellular signaling pathways such as MAPK and NF-κB, and triggering inflammation and release of pro-inflammatory cytokines [54]. However, treatment with antioxidants or coating NMs with antioxidant drugs has been shown to rescue NM-induced cellular oxidative stress [55,56]. For example, QDs induced oxidative stress in cells can be prevented by either treating cells or modifying the QDs with antioxidant drugs, such as N-acetylcysteine and lipoic acid [26,55,57].…”

“…However, treatment with antioxidants or coating NMs with antioxidant drugs has been shown to rescue NM-induced cellular oxidative stress [55,56]. For example, QDs induced oxidative stress in cells can be prevented by either treating cells or modifying the QDs with antioxidant drugs, such as N-acetylcysteine and lipoic acid [26,55,57]. Damaged DNA is rescued by DNA repair mechanisms in the cell, thereby maintaining genomic stability, failing which carcinogenesis may result [37].…”