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InP/ZnS quantum dots (QDs) are an emerging option in QD technologies for uses of fluorescent imaging as well as targeted drug and anticancer therapies based on their customizable properties. In this study we explored effects of InP/ZnS when treated with HeLa cervical cancer cells. We employed XTT viability assays, reactive oxygen species (ROS) analysis, and apoptosis analysis to better understand cytotoxicity extents at different concentrations of InP/ZnS. In addition, we compared the transcriptome profile from the QD-treated HeLa cells with that of untreated HeLa cells to identify changes to the transcriptome in response to the QD. RT-qPCR assay was performed to confirm the findings of transcriptome analysis, and the QD mode of action was illustrated. Our study determined both IC50 concentration of 69 &micro, g/mL and MIC concentration of 167 &micro, g/mL of InP/ZnS. It was observed via XTT assay that cell viability was decreased significantly at the MIC. Production of superoxide, measured by ROS assay with flow cytometry, was decreased, whereas levels of nitrogen radicals increased. Using analysis of apoptosis, we found that induced cell death in the QD-treated samples was shown to be significantly increased when compared to untreated cells. We conclude InP/ZnS QD to decrease cell viability by inducing stress via ROS levels, apoptosis induction, and alteration of transcriptome.

Among cationic polymers, chitosan (CS) is a promising non-viral vector due to its biocompatibility, biodegradability and safety profile. However, its application for gene delivery is hindered by its poor solubility at physiological pH. In this study, novel water-soluble chitosan derivatives containing triethylphosphonium chloride ((N-(1-carboxybutyl-4-triethylphosphonium chloride) chitosan = TEPB-CS)) or triethylammonium chloride ((N-(1-carboxybutyl-4-triethylammonium chloride) chitosan = TEAB-CS)) with 4-carbon spacers separating the cationic units from the chitosan backbone were synthesized by carbodiimide mediated coupling reactions. Two different degrees of substitution of quaternary phosphonium (43% and 21%) and ammonium (40.6% and 26%) were synthesized. The polymers with higher degrees of substitutions displayed higher solubility in aqueous media and were further grafted with mPEG (TEAB-CS-g-mPEG and TEPB-CS-g-mPEG) and used for DNA complexation, cytotoxicity, apoptosis, and gene transfection studies. Chemical characterization of the above polymers was performed by FTIR, 1H NMR, and 31P NMR, and the degree of substitution of the grafted phosphonium and ammonium and mPEG was calculated by 1H NMR. The polymers efficiently bound pDNA at weight ratio of polymer:pDNA of 2.8:1. From dynamic light scattering experiments, the mean diameters of the calf thymus DNA complexes with the polymers, in water and phosphate buffer (pH 7.4), were in the range of 140 – 330 nm. Zeta potential of these complexes in water became positive as the weight ratios of the polymers/DNA exceeded 2:1. Most of these polymers mildly affect the viability of HeLa cells with a final concentration of 10 µg/mL or higher. Cell viability was only modestly compromised in the presence of 100 µg/mL of TEPB-CS-g-mPEG, and this derivative was also found to display the highest transfection efficiencies among all four polymers. Apoptosis measurements by flow cytometry indicated that both TEAB-CS-g-mPEG and TEPB-CS-g-mPEG induce no perceptible and mild apoptosis with their concentration at 100 µg/mL, respectively. Together, the present study provides evidence that these PEGylated TEPB-CS and TEAB-CS are safe and effective vectors for efficient nucleic acid delivery.

Next-generation sequencing (NGS) technology has revolutionized sequence-based research. In recent years, high-throughput sequencing has become the method of choice in studying the toxicity of chemical agents through observing and measuring changes in transcript levels. Engineered nanomaterial (ENM)-toxicity has become a major field of research and has adopted microarray and newer RNA-Seq methods. Recently, nanotechnology has become a promising tool in the diagnosis and treatment of several diseases in humans. However, due to their high stability, they are likely capable of remaining in the body and environment for long periods of time. Their mechanisms of toxicity and long-lasting effects on our health is still poorly understood. This review explores the effects of three ENMs including carbon nanotubes (CNTs), quantum dots (QDs), and Ag nanoparticles (AgNPs) by cross examining publications on transcriptomic changes induced by these nanomaterials.