The Role of Cadmium and Nickel in Estrogen Receptor Signaling and Breast Cancer: Metalloestrogens or Not?

During the last half-century, incidences of breast cancer have increased globally. Various factors —genetic and environmental— have been implicated in the initiation and progression of this disease. One potential environmental risk factor that has not received a lot of attention is the exposure to heavy metals. While several mechanisms have been put forth describing how high concentrations of heavy metals play a role in carcinogenesis, it is unclear whether chronic, lowlevel exposure to certain heavy metals (i.e. cadmium and nickel), can directly result in the development and progression of cancer. Cadmium and nickel have been hypothesized to play a role in breast cancer development by acting as metalloestrogens— metals that bind to estrogen receptors and mimic the actions of estrogen. Since the lifetime exposure to estrogen is a wellestablished risk factor for breast cancer, anything that mimics its activity will likely contribute to the etiology of the disease. However, heavy metals, depending on their concentration, are capable of binding to a variety of proteins and may exert their toxicities by disrupting multiple cellular functions, complicating the analysis of whether heavy metal-induced carcinogenesis is mediated by the estrogen receptor. The purpose of this review is to discuss the various epidemiological, in vivo, and in vitro studies that show a link between the heavy metals, cadmium and nickel, and breast cancer development. We will particularly focus on the studies that test whether or not these two metals act as metalloestrogens in order to assess the strength of the data supporting this hypothesis

Polymeric nanocarriers for controlled and enhanced delivery of therapeutic agents to the CNS

Polymeric nanocarriers are versatile structures that can be engineered to obtain high drug loading, good delivery yields and tunable release kinetics. Moreover, the particle surface can be modified for selective targeting of organs or tissues. In particular, polymeric nanocarriers can be conjugated with functional groups promoting translocation through the blood–brain barrier, thus providing a promising system to deliver therapeutic agents and/or diagnostic probes to the brain. Here we review recent literature on the preparation and characterization of polymeric nanoparticles as potential agents for drug delivery to the CNS, with an emphasis on materials chemistry and functionalization strategies for improved selectivity and delivery. Finally, we underline the immunotoxicological aspects of this class of nanostructured materials in view of potential clinical applications

The use of ex vivo ovary culture for assessment of alterations in steroidogenesis following neonatal exposure to poly(ethylene glycol)-block-polylactide methyl ether or titanium dioxide nanoparticles in Wistar rats

Objectives. Rapid development and widespread application of different types of nanoparticles (NPs) may result in increased exposure of humans and animals to NPs. Recently, reproductive toxicity due to NP exposure has become a major component of risk assessment. Current data have suggested that NPs may pose adverse effects on male and female reproductive health by altering normal testis and ovarian structure, and sex hormone levels. To detect possible alterations in steroidogenesis in adult and infantile rats following neonatal exposure to polymeric poly(ethylene glycol)-block-polylactide methyl ether (PEG-b-PLA) or titanium dioxide (TiO2) NPs, whole ovary cultures were used

Adverse eff ects of polymeric nanoparticle poly(ethylene glycol)- block-polylactide methyl ether (PEG-b-PLA) on steroid hormone secretion by porcine granulosa cells

Objectives. Development of nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. Diverse effects of different type NPs relating to mammalian reproductive tissues have been demonstrated. Th e objective of this study was to explore the in vitro effects of polymeric nanoparticle poly(ethylene glycol)-blockpolylactide methyl ether (PEG-b-PLA NPs) on functional state and viability of ovarian granulosa cells (GCs), which play an important role in maintaining ovarian function and female fertility

Gold and titania nanoparticles accumulated in the body induce late toxic effects and alterations in transcriptional and miRNA landscape

The growing production of nanomaterials and their presence in consumer products raises fear about their impact on human health and the environment. Of particular concern are those nanomaterials that exhibit poor excretion and tend to accumulate in living organisms. Our study investigated the potential adverse biological effects of residual gold and titania nanoparticles (PEG-AuNPs and TiONPs) 28 days after a single intravenous administration in rats. To comprehensively assess the potential health hazard of these metal nanoparticles (MNP), toxicological and transcriptomic analyses were employed. The liver was the primary organ of the MNP deposition, causing a reduction in the relative liver weight compared to unexposed animals. Concurrently, changes in serum biomarkers indicative of hepatic dysfunction and hematological and immunological alternations were determined. Integrated transcriptomic analysis unveiled exposure-induced effects on the rats' lungs, liver, and kidneys. The hepatic tissue, particularly in PEG-AuNPs-exposed rats, exhibited a noteworthy prevalence of deregulated genes, with functional classification spanning lipid metabolism, cell cycle, and cell proliferation pathways. Although the number of deregulated miRNAs was relatively modest compared to mRNA expression changes, both types of MNPs deregulated miR-203a, associated with liver injury, and miR-18a-5p and miR-32-5p linked to kidney damage. This study underscores the imperative for a more exhaustive biosafety assessment of poorly soluble MNPs that tend to deposit in the body. Such investigations are crucial for delineating the potential risks of these nanomaterials and guiding the development of adequate safety measures in their production and usage