Cytotoxicity Of Quantum Dots Research Articles

Graphene quantum dots in alveolar macrophage: uptake-exocytosis, accumulation in nuclei, nuclear responses and DNA cleavage

BackgroundGiven the tremendous potential for graphene quantum dots (QDs) in biomedical applications, a thorough understanding of the interaction of these materials with macrophages is essential because macrophages are one of the most important barriers against exogenous particles. Although the cytotoxicity and cellular uptake of graphene QDs were reported in previous studies, the interaction between nuclei and the internalized graphene QDs is not well understood. We thus systematically studied the nuclear uptake and related nuclear response associated with aminated graphene QDs (AG-QDs) exposure.ResultsAG-QDs showed modest 24-h inhibition to rat alveolar macrophages (NR8383), with a minimum inhibitory concentration (MIC) of 200 μg/mL. Early apoptosis was significantly increased by AG-QDs (100 and 200 μg/mL) exposure and played a major role in cell death. The internalization of AG-QDs was mainly via energy-dependent endocytosis, phagocytosis and caveolae-mediated endocytosis. After a 48-h clearance period, more than half of the internalized AG-QDs remained in the cellular cytoplasm and nucleus. Moreover, AG-QDs were effectively accumulated in nucleus and were likely regulated by two nuclear pore complexes genes (Kapβ2 and Nup98). AG-QDs were shown to alter the morphology, area, viability and nuclear components of exposed cells. Significant cleavage and cross-linking of DNA chains after AG-QDs exposure were confirmed by atomic force microscopy investigation. Molecular docking simulations showed that H-bonding and π-π stacking were the dominant forces mediating the interactions between AG-QDs and DNA, and were the important mechanisms resulting in DNA chain cleavage. In addition, the generation of reactive oxygen species (ROS) (e.g., •OH), and the up-regulation of caspase genes also contributed to DNA cleavage.ConclusionsAG-QDs were internalized by macrophages and accumulated in nuclei, which further resulted in nuclear damage and DNA cleavage. It is demonstrated that oxidative damage, direct contact via H-bonding and π-π stacking, and the up-regulation of caspase genes are the primary mechanisms for the observed DNA cleavage by AG-QDs.

Preparation of Photoluminescent Molybdenum Disulfide Quantum Dots for Biomedical Imaging

Since the discovery of graphene, great attention has been paid to transition metal disulfide two-dimensional layered materials due to their exceptional physical and chemical properties. Recently, molybdenum disulfide (MoS2) quantum dots (QDs) have been extensively investigated because of their unique quantum confinement and boundary effects as well as potential applications in fluorescence imaging, electrochemical catalysis, and biosensors. The preparation of MoS2 quantum dots can be divided into two types: bottom-up method and top-down method. In order to prepare aqueous MoS2 QDs solution, in this study, we develop a bottom-up strategy to synthesize MoS2 QDs using a simple, one-step hydrothermal method with ammonium tetrathiomolybdate [(NH4)2MoS4] as the precursor and hydrazine hydrate as the reducing agent. The morphology and structural characteristics of MoS2 QDs are analyzed by transmission electron microscopy, and optical properties are characterized using UV-Vis and photoluminescence spectroscopy. Also, the cytotoxicity of MoS2 QDs are tested. Experimental results demonstrate that MoS2 QDs can be used for biomedical imaging and drug delivery carriers.

Preparation of Photoluminescent Molybdenum Disulfide Quantum Dots for Biomedical Imaging

Recently, molybdenum disulfide (MoS2) quantum dots (QDs) have been extensively investigated because of their unique quantum confinement and boundary effects as well as potential applications in fluorescence imaging, electrochemical catalysis, and biosensors. In this study, we synthesize MoS2 QDs by using a one-step hydrothermal method with ammonium tetrathiomolybdate as the precursor and hydrazine hydrate as the reducing agent. The morphology and structural characteristics of MoS2 QDs are analyzed by transmission electron microscopy, and optical properties are characterized using UV-Vis absorption and photoluminescence spectroscopy. The cytotoxicity of MoS2 QDs is tested by MTT assay. MoS2 QDs in biomedical imaging is demonstrated by a simple incubation study with U251 cells. Experimental results demonstrate that MoS2 QDs can be used for biomedical imaging applications.

Dysfunction of various organelles provokes multiple cell death after quantum dot exposure.

Quantum dots (QDs) are different from the materials with the micrometer scale. Owing to the superiority in fluorescence and optical stability, QDs act as possible diagnostic and therapeutic tools for application in biomedical field. However, potential threats of QDs to human health hamper their wide utilization in life sciences. It has been reported that oxidative stress and inflammation are involved in toxicity caused by QDs. Recently, accumulating research unveiled that disturbance of subcellular structures plays a magnificent role in cytotoxicity of QDs. Diverse organelles would collapse during QD treatment, including DNA damage, endoplasmic reticulum stress, mitochondrial dysfunction and lysosomal rupture. Different forms of cellular end points on the basis of recent research have been concluded. Apart from apoptosis and autophagy, a new form of cell death termed pyroptosis, which is finely orchestrated by inflammasome complex and gasdermin family with secretion of interleukin-1 beta and interleukin-18, was also summarized. Finally, several potential cellular signaling pathways were also listed. Activation of Toll-like receptor-4/myeloid differentiation primary response 88, nuclear factor kappa-light-chain-enhancer of activated B cells and NACHT, LRR and PYD domains-containing protein 3 inflammasome pathways by QD exposure is associated with regulation of cellular processes. With the development of QDs, toxicity evaluation is far behind its development, where specific mechanisms of toxic effects are not clearly defined. Further studies concerned with this promising area are urgently required.

Proficient surface modification of CdSe quantum dots for highly luminescent and biocompatible probes for bioimaging: A comparative experimental investigation

The cytotoxicity of Cd based Quantum dots (QDs) is major concern that hinders their practical use in bioimaging. Therefore, the objective of first of its kind report is to overcome this hindrance where the comparative cytotoxicity study of poly CdSe, CdSe QDs, CdSe/ZnS QDs and CdSe QDs encapsulated by TEOS, polyvinylalcohal and polyethylene glycol being presented. All the QD were synthesized and encapsulated by wet chemical method and studied. Prepared QDs were monodispersed, spherical in shape and exhibited size range of 1.8–2.2 nm. Elemental analysis confirms the formation of CdSe QDs and other mentioned structures. Surface functional groups notify the biocompatibility of core-shell and encapsulated QDs with respect to poly and bare CdSe QDs. Cytotoxicity of QDs was analyzed using human embryonic kidney cell line. Encapsulated QDs were tested even at very high concentrations and for long incubation time of 24 h and even upto 72 h of incubation. Core-shell and encapsulated QDs acquire excellent monochromatic luminescence intensity and negligible cytotoxicity as compared to prepared poly CdSe and bare CdSe QDs thus can be used as luminescent probes for bioimaging.

Comparative studies of biological activity of cadmium-based quantum dots with different surface modifications

This paper presents a modification of the surface of CdS/ZnS and CdSexS1−x/ZnS quantum dots (QDs) with 3-mercaptopropionic and 6-mercaptohexanoic acid. The obtained QDs were characterized using TEM, DLS, UV–Vis, and fluorescence spectroscopy. Flow cytometry was applied to evaluate the cytotoxicity of QDs and examine the type of death caused by the tested nanoparticles. In addition, the generation of reactive oxygen species after incubation of the tested cells with CdSexS1−x/ZnS–MPA and CdSexS1−x/ZnS–MHA QDs was evaluated. The study was conducted on three cell lines: adherent (A549 and MRC-5) and suspension ones (K562). The conducted research demonstrated that the tested nanoparticles exhibit concentration-dependent toxicity. It was observed that the surface modification influences the toxicity level of the examined QDs, and modification of their surface with the use of the ligand of longer carbon chain (MHA) reduces the toxicity in comparison with QDs–MPA. It was also found that all tested QDs caused the death of cells in the course of necrosis. Based on obtained results, it was concluded that the cytotoxicity of QDs is to a large extent related to reactive oxygen species (ROS) generation.

Chip-based magnetic solid phase microextraction coupled with ICP-MS for the determination of Cd and Se in HepG2 cells incubated with CdSe quantum dots

The quantification of trace Cd and Se in cells incubated with CdSe quantum dots (QDs) is critical to investigate the cytotoxicity of CdSe QDs. In this work, a miniaturized platform, namely chip-based magnetic solid phase microextraction (MSPME) packing with sulfhydryl group functionalized magnetic nanoparticles, was fabricated and combined with inductively coupled plasma mass spectrometry (ICP-MS) for the determination of trace Cd and Se in cells. Under the optimized conditions, the limits of detection (LOD) of the developed chip-based MSPME-ICP-MS system are 2.2 and 21ngL−1 for Cd and Se, respectively. The proposed method is applied successfully to the analysis of total and released small molecular fraction of Cd and Se in Human hepatocellular carcinoma cells (HepG2 cells) incubated with CdSe QDs, and the recoveries for the spiked samples are in the range of 86.0–109%. This method shows great promise to analyze cell samples and the obtained results are instructive to explore the cytotoxicity mechanism of CdSe QDs in cells.

Dextran microgels loaded with ZnO QDs: pH‐triggered degradation under acidic conditions

ABSTRACTWe demonstrated an extremely facile way to fabricate inorganic–organic microgels with pH sensitivity and fluorescence. Aqueous dextran microgels are crosslinked by ZnO quantum dots (QDs). The ZnO@Dextran microgels were synthesized by simply mixing amino‐modified ZnO (ZnO QDs) with carboxymethyl dextran (CMD) while stirring. The hybrid microgels showed an average diameter of ∼5 μm and strong fluorescence under ultraviolet (365 nm) irradiation. Up to 79.3 wt % of ZnO QDs were loaded into microgels. The ZnO QDs crosslinkage in the hybrid microgels structure enabled the microgels to degrade under mild acidic environment due to pH sensitivity of ZnO QDs. After loading of doxorubicin (Dox), the microgels were used as drug carriers for pH‐controlled release of Dox. The degradation of the microgels and the release of loaded cargos could be monitored by detecting fluorescence intensity of the microgels. Moreover, owing to the cytotoxicity of ZnO QDs at their destination, drug‐loaded ZnO@Dextran microgels can be used for synergistic therapy. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45831.

Gelatin stabilization of quantum dots for improved stability and biocompatibility

We herein report an aqueous synthesis of gelatin stabilized CdTe/CdS/ZnS (CSSG) core/double shell quantum dots (QDs) with improved biocompatibility. The as-synthesized QDs were characterized by ultraviolet-visible (UV–vis) and photoluminescence (PL) spectroscopic techniques, x-ray diffraction technique (XRD), x-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The CSSG QDs revealed high photoluminescence quantum yield (PLQY) with excellent stability over a period of one year and retained 90% of its initial PLQY without any aggregation or precipitation under ambient condition. The cell viability study conducted on HeLa, cervical cancer cell lines indicated that the gelatin stabilization effectively decreased the QDs cytotoxicity by about 50%. The CSSG QDs were conjugated with transferrin (Tf) for the efficient delivery to the cancer cells followed by fluorescence imaging. The results showed that the CSSG QDs illuminates the entire cell which renders the QDs as cell labeling markers. The gelatin stabilized core/double shell QDs are potential candidates for long time fluorescent bio-imaging.

Enantioselective cytotoxicity of ZnS:Mn quantum dots in A549 cells.

Chirality strongly influences many biological properties of materials, such as cell accumulation, enzymatic activity, and toxicity. In the past decade, it has been shown that quantum dots (QDs), fluorescent semiconductor nanoparticles with unique optical properties, can demonstrate optical activity due to chiral ligands bound on their surface. Optically active QDs could find potential applications in biomedical research, therapy, and diagnostics. Consequently, it is very important to investigate the interaction of QDs capped with chiral ligands with living cells. The aim of our study was to investigate the influence of the induced chirality of Mn-doped ZnS QDs on the viability of A549 cells. These QDs were stabilized with D- and L-cysteine using a ligand exchange technique. The optical properties of QDs were studied using UV-Vis, photoluminescence (PL), and circular dichroism (CD) spectroscopy. The cytotoxicity of QDs was investigated by high content screening analysis. It was found that QDs stabilized by opposite ligand enantiomers, had identical PL and UV-Vis spectra and mirror-imaged CD spectra, but displayed different cytotoxicity: QDs capped with D-cysteine had greater cytotoxicity than L-cysteine capped QDs.

Gelatin nanoparticles: a potential candidate for medical applications

AbstractGelatin is a protein obtained from the hydrolysis of collagen. Gelatin is an attractive biodegradable material for use in nano-biotechnology and nano-pharmaceutics. Gelatin nanoparticles (NPs) have been widely used as drug and gene carrier to targeted sick tissues including cancer, tuberculosis, HIV infection along with the treatment of vasospasm and restenosis, due to its biocompatibility and biodegradability. For instance, coating with gelatin lowers the cytotoxicity of quantum dots. Moreover, gelatin NPs have the ability to cross the blood-brain barrier, hence proven as a promising candidate to target brain disorders. Macrophage targeting with gelatin NPs for remedy of different diseases is repeatedly reported in previous years. In tissue engineering gelatin is actively utilized for construction of biological and life-long 3D scaffolds for bio-artificial tissues and organ production. Gelatins have a wide range of potential applications which needs to be unraveled in more detail. This review is mainly focused on the applications of gelatin NPs in biomedical sciences.

Effects of surface modification of quantum dots on viability and migration of triple-negative breast cancer cells

Triple-negative breast cancer (BC) shows strong metastasis and has a bad prognosis. There are few effective approaches until date to detect BC cells at an early stage. Quantum dots (QDs) are one of the most promising nanomaterials for the detection of BC cells. QDs are usually modified with some functional molecules, such as PEG and BSA, to decrease or possibly eliminate their toxicity. Although a large number of studies have investigated the cytotoxicity of QDs, the effects of surface modification of QDs on biological behaviors of triple-negative BC cells remain unclear. In this work, QDs were prepared using the hydrothermal method and chemically modified with PEG and BSA. The optical performance of QDs was recorded with a digital camera. Their absorption and fluorescence (FL) properties were analyzed by UV–Vis spectrometer and FL spectrophotometer, respectively. The effects of QDs and surface modification on viability and migration were principally investigated. The possible mechanism was primarily analyzed. The results show that QDs exhibit excellent optical performance under ultraviolet irradiation. Surface modification slightly reduces the photon count reaching the QDs surface. Moreover, surface modification results in a blue-shift of FL peak of QDs, which is ascribed to the change in surface chemical environment because of PEG and BSA modifications. In addition, QDs, PEG coated QDs (PEG@CdTe) and BSA coated QDs (BSA@CdTe) can reduce viability and inhibit migration of BC cells. The inhibition effects are time- and concentration-dependent. In addition, PEG and BSA modified QDs exhibit lower inhibition effects on BC cells, as compared with unmodified QDs. In this process, Reactive oxygen species (ROS) does not appear to play an important role, and other pathways should be considered. This work provides experimental support and useful clinical guidance for QDs-applications in BC detection.

Effective improvement in optical properties of colloidal CdTe@ZnS quantum dots synthesized from aqueous solution

Efficient synthesis of high-quality quantum dots (QDs) with excellent optical properties by aqueous synthesis is still of great significance for extended optical applications. Herein we highlight the advantages in optical properties of colloidal CdTe@ZnS QDs prepared by a facile and highly effective aqueous synthesis method. These achievements were realized by delicate manipulation of the conditions involved in nucleation and the growth process. Transmission electron microscopy (TEM) images indicated the QDs were uniform size and well dispersible. The emission peaks of the as-prepared QDs could shift from 496 to 698 nm with narrow full width at half maximum (FWHM), and the corresponding fluorescent color changed from green to red. Moreover, the emission could even reach to the near-infrared (NIR) region (706–796 nm) by extending the reaction time. The highest photoluminescence (PL) quantum yield (QY) of the QDs could reach to 60%, and the average of FWHM was about 55 nm. To address the problem of wide size-distribution in PL QY decrease and FWHM broadening, the colloids of QDs prepared at long reaction time (above 3 h) were centrifuged (12 000 r min−1). In addition, the assessment of QD cytotoxicity indicated the CdTe@ZnS QDs were much less cytotoxic and showed good biocompatibility. Compared with organic synthesis, our aqueous synthesis of QDs could be carried out efficiently on a large scale and showed good batch-to-batch reproducibility. The as-prepared CdTe@ZnS QDs exhibited excellent optical properties and hold a good potential to be applied in optoelectronic and biological applications.

Chemically synthesized CdSe quantum dots inhibit growth of human lung carcinoma cells via ROS generation.

Quantum dots (QDs), semiconducting materials have potential applications in the field of electronic and biomedical applications including cancer therapy. In present study, cadmium selenide (CdSe) QDs were synthesized by chemical method. Octadecene was used as non-coordinating solvent which facilitated the formation of colloidal solutions of nanoparticles. CdSe QDs were characterized by UV-vis spectrometer and transmission electron microscope (TEM). The size measured by TEM was varied between 2-5 nm depending upon temperature. The cytotoxic activity of QDs was monitored by MTT assay, nuclear condensation, ROS activity and DNA fragmentation assay on human lung epithelial A549 cell line. Cells were treated with different concentrations of varying size of CdSe QDs for 24 h. CdSe QDs induced significant (p < 0.05) dose dependent cytotoxicity and this was comparable to the sizes of particles. Smaller particles were more cytotoxic to the large particles. Fluorescence microscopic analysis revealed that QDs induced oxidative stress generating significant ROS level and consequently, induced nuclear condensation and DNA fragmentation. Study suggested the cytotoxicity of CdSe QDs via ROS generation and DNA fragmentation depending upon particles size.

Biotoxicity of CdS/CdSe Core-Shell Nano-Structures

The cytotoxicity of hydrophobic QDs CdS/CdSe was tested assigning MTT assay on Human Embryonic Kidney cells (HEK-293), breast cancer cells (MCF-7) and Enrichlish Ascitices Cells (EAC). Approximately 65% bio-toxicity was observed in MCF-7 for the core-shell QDs. These QDs may also find effective applications in other optoelectronic devices. CdS/CdSe core-shell hetrostructure quantum dots (QDs) were generated by chemical reaction between the respective chalcogens and cadmium metal salt. Sulphur powder was utilized for CdS core preparation while selenium was extracted from an organoselenium compound to impart CdSe shell layer at a temperature between 150℃ - 200℃. So-prepared core-shell QDs showed good optical properties. The particle size was found to be in the range of 3 - 4 nm with spherical morphology and cubic crystal structure.

Multifunctional Mesoporous Silica Nanoparticles Based on Charge-Reversal Plug-Gate Nanovalves and Acid-Decomposable ZnO Quantum Dots for Intracellular Drug Delivery.

A novel type of pH-responsive multifunctional mesoporous silica nanoparticle (MSN) was developed for cancerous cells drug delivery and synergistic therapy of tumor. MSNs were covered with a kind of cell-penetrating peptide, deca-lysine sequence (K10), to enhance their escape from the endosomes. After K10's primary amines were reacted with citraconic anhydride to form acid-labile β-carboxylic amides, zinc oxide (ZnO) quantum dots (QDs) were introduced to cap MSNs via electrostatic interaction. The obtained ZnO@MSN drug-delivery system (DDS) achieves "zero-premature" drug release under a physiological environment. However, once the DDS is transferred to the cancerous cells' acidic endosome, ZnO QDs would rapidly dissolve and the acid-labile amides on the side chain of K10 would hydrolyze to regenerate primary amines, resulting in the uncapping of MSNs and exposure of the cell-penetrating peptide K10. The regenerated K10 could help the DDS escape from the endosome and efficiently release the loaded drugs inside the cells. At the meantime, because of the cytotoxicity of ZnO QDs at their destination, the ZnO@MSN DDS may achieve a synergistic antitumor effect to improve the therapeutic index.

Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity.

The potential cytotoxicity of cadmium selenide (CdSe) quantum dots (QDs) presents a barrier to their use in biomedical imaging or as diagnostic and therapeutic agents. Sulforaphane (SFN) is a chemoprotective compound derived from cruciferous vegetables which can up-regulate antioxidant enzymes and induce apoptosis and autophagy. This study reports the effects of SFN on CdSe QD-induced cytotoxicity in immortalised human hepatocytes and in the livers of mice. CdSe QDs induced dose-dependent cell death in hepatocytes with an IC50 = 20.4 μM. Pre-treatment with SFN (5 μM) increased cell viability in response to CdSe QDs (20 μM) from 49.5 to 89.3%. SFN induced a pro-oxidant effect characterized by depletion of intracellular reduced glutathione during short term exposure (3–6 h), followed by up-regulation of antioxidant enzymes and glutathione levels at 24 h. SFN also caused Nrf2 translocation into the nucleus, up-regulation of antioxidant enzymes and autophagy. siRNA knockdown of Nrf2 suggests that the Nrf2 pathway plays a role in the protection against CdSe QD-induced cell death. Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death. Moreover, the role of autophagy in SFN protection against CdSe QD-induced cell death was confirmed using mouse embryonic fibroblasts lacking ATG5. CdSe QDs caused significant liver damage in mice, and this was decreased by SFN treatment. In conclusion, SFN attenuated the cytotoxicity of CdSe QDs in both human hepatocytes and in the mouse liver, and this protection was associated with the induction of Nrf2 pathway and autophagy.

Quantum Dots Encapsulated with Canine Parvovirus-Like Particles Improving the Cellular Targeted Labeling.

Quantum dots (QDs) have a promising prospect in live-cell imaging and sensing because of unique fluorescence features. QDs aroused significant interest in the bio-imaging field through integrating the fluorescence properties of QDs and the delivery function of biomaterial. The natural tropism of Canine Parvovirus (CPV) to the transferrin receptor can target specific cells to increase the targeting ability of QDs in cell imaging. CPV virus-like particles (VLPs) from the expression of the CPV-VP2 capsid protein in a prokaryotic expression system were examined to encapsulate the QDs and deliver to cells with an expressed transferrin receptor. CPV-VLPs were used to encapsulate QDs that were modified using 3-mercaptopropionic acid. Gel electrophoresis, fluorescence spectrum, particle size, and transmission electron microscopy verified the conformation of a complex, in which QDs were encapsulated in CPV-VLPs (CPV-VLPs-QDs). When incubated with different cell lines, CPV-VLPs-QDs significantly reduced the cytotoxicity of QDs and selectively labeled the cells with high-level transferrin receptors. Cell-targeted labeling was achieved by utilizing the specific binding between the CPV capsid protein VP2 of VLPs and cellular receptors. CPV-VLPs-QDs, which can mimic the native CPV infection, can recognize and attach to the transferrin receptors on cellular membrane. Therefore, CPV-VLPs can be used as carriers to facilitate the targeted delivery of encapsulated nanomaterials into cells via receptor-mediated pathways. This study confirmed that CPV-VLPs can significantly promote the biocompatibility of nanomaterials and could expand the application of CPV-VLPs in biological medicine.

An experimental and theoretical assessment of quantum dot cytotoxicity

Scheme represents the model approach. After exposure to quantum dots initial cell population may follow various pathways which depend on intracellular concentration of quantum dots.

Continuing progress toward controlled intracellular delivery of semiconductor quantum dots.

The biological applications of luminescent semiconductor quantum dots (QDs) continue to grow at a nearly unabated pace. This growth is driven, in part, by their unique photophysical and physicochemical properties which have allowed them to be used in many different roles in cellular biology including: as superior fluorophores for a wide variety of cellular labeling applications; as active platforms for assembly of nanoscale sensors; and, more recently, as a powerful tool to understand the mechanisms of nanoparticle mediated drug delivery. Given that controlled cellular delivery is at the intersection of all these applications, the latest progress in delivering QDs to cells is examined here. A brief discussion of relevant considerations including the importance of materials preparation and bioconjugation along with the continuing issue of endosomal sequestration is initially provided for context. Methods for the cellular delivery of QDs are then highlighted including those based on passive exposure, facilitated strategies that utilize peptides or polymers and fully active modalities such as electroporation and other mechanically based methods. Following on this, the exciting advent of QD cellular delivery using multiple or combined mechanisms is then previewed. Several recent methods reporting endosomal escape of QD materials in cells are also examined in detail with a focus on the mechanisms by which access to the cytosol is achieved. The ongoing debate over QD cytotoxicity is also discussed along with a perspective on how this field will continue to evolve in the future.