Formulation, characterization, and in vitro evaluation of quantum dots loaded in poly(lactide)-vitamin E TPGS nanoparticles for cellular and molecular imaging

We developed a novel system of poly(lactide acid)-d-alpha-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) nanoparticles (NPs) for quantum dots (QDs) formulation to improve imaging effects and reduce side effects as well as to promote a sustainable imaging. The QDs-loaded PLA-TPGS NPs were prepared by a modified solvent extraction/evaporation method, which were then characterized by laser light scattering (LLS) for size and size distribution; field emission scanning electron microscopy (FESEM), atomic force microscopy (AFM) and transmission electron microscope (TEM) for surface morphology. Surface chemistry of the QDs-loaded PLA-TPGS NPs was analyzed by X-ray photoelectron microscopy (XPS) and Fourier transform infra-red spectroscopy (FTIR). Encapsulation efficiency of the QDs in the polymeric nanoparticles was measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The photostability of the QDs formulated in the PLA-TPGS nanoparticles was investigated as changes in the florescence intensity versus the irradiation time. Confocal laser scanning microscopy (CLSM) was used to image the cellular uptake of the QDs-loaded NPs by MCF-7 cells. Methylthiazolyldiphenyl-tetrazolium (MTT) assay was employed to assess the viability of MCF-7 cells incubated with the QDs formulated by the PLA-TPGS NPs versus the mercaptoacetic acid (MAA)-coated QDs. It was found that the QDs formulated in the PLA-TPGS NPs can result in higher fluorescence intensity and higher photostability than the bare QDs as well as lower cytotoxicity than the MAA-coated QDs.     

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.     

Untargeted quantum dots in confocal microscopy of living cells

The problem of the nonspecific binding of quantum dots (QDs) with cells is very important, but not fully understood taking into account the possible application of QDs in medical and fundamental studies. The interactions of untargeted CdSe/ZnS QDs with isolated frog muscle fibers, HeLa cells, and J774 cells were investigated. The observations were made on living cells using laser confocal microscopy (Leica TCS SL). QDs covered with polyethylene glycol without any functional reactive groups with an emission maximum at 565 nm were used in the study. This type of QD is suggested to prevent the interaction of QDs with biological molecules. It has been shown that QDs do not enter HeLa cells, the T-system, or the sarcoplasm of skeletal muscle fibers. However, during long-term incubation, J774 cells can take up QDs. The obtained data demonstrated the diversity of interactions of untargeted QDs with different cell types and are important for understanding problems of nonselective uptake and cytotoxicity of QDs.     

Cytotoxicity of CdSe-based quantum dots incorporated in glass nanoparticles evaluated using human keratinocyte HaCaT cells

CdSe quantum dots (QDs) are potential fluorescent reagents, but leakage of Cd and Se often induces cytotoxicity. Here we prepared CdSe-based QDs with glass to reduce their leakage and examined their cytotoxicity using keratinocyte cells. The cytotoxicity of the QDs with glass was obviously lower than that of the commercial QDs with polymer, suggesting their safety for biological applications.     

Characterization and cancer cell targeted imaging properties of human antivascular endothelial growth factor monoclonal antibody conjugated CdTe/ZnS quantum dots

High luminescence quantum yield water‐soluble CdTe/ZnS core/shell quantum dots (QDs) stabilized with thioglycolic acid were synthesized. QDs were chemically coupled to fully humanized antivascular endothelial growth factor₁₆₅ monoclonal antibodies to produce fluorescent probes. These probes can be used to assay the biological affinity of the antibody. The properties of QDs conjugated to an antibody were characterized by ultraviolet and visible spectrophotometry, fluorescent spectrophotometry, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, transmission electron microscopy and fluorescence microscopy. Cell‐targeted imaging was performed in human breast cancer cell lines. The cytotoxicity of bare QDs and fluorescent probes was evaluated in the MCF‐7 cells with an MTT viability assay. The results proved that CdTe/ZnS QD–monoclonal antibody nanoprobes had been successfully prepared with excellent spectral properties in target detections. Surface modification by ZnS shell could mitigate the cytotoxicity of cadmium‐based QDs. The therapeutic effects of antivascular endothelial growth factor antibodies towards cultured human cancer cells were confirmed by MTT assay. Copyright © 2014 John Wiley & Sons, Ltd.     

Studies on the induction and expression of T cell-mediated immunity. XIV. Antigen-nonspecific oxidation-dependent cellular cytotoxicity (ODCC) mediated by sodium periodate oxidation of cytotoxic T lymphocytes

Alloimmune murine thymus-derived cytotoxic lymphocytes (CTL) generated in vivo or in vitro are shown to lyse antigen-nonspecific target cells (tumor cells, Con A, and LPS blasts) following treatment of CTL with an oxidizing agent, sodium periodate (NaIO4). It has been shown that NaIO4 oxidizes terminal sialic acid residues of cell surface macromolecules. The presence of reactive aldehyde groups, generated by NaIO4 modification, is required for the expression of antigen-nonspecific cytotoxicity because treatment of modified cells with a reducing agent such as potassium borohydride (KBH4) resulted in the abrogation of cytotoxicity. However, KBH4 treatment of unmodified or NaIO4-modified CTL has no effect on antigen-specific cytotoxicity. The modification of CTL by NaIO4 is sufficient to lead to the formation of lymphocyte-target cell conjugates and lysis of bound targets. Monoclonal antibodies directed against the Lyt-2 antigens of CTL, but not Lyt-1 antigens, in the absence of complement inhibited the nonspecific cytotoxicity resulting from NaIO4 modification of effector lymphocytes. These findings suggest that the mere interaction with or perturbation of appropriate cell surface molecule(s) of effector lymphocytes such as Lyt antigens by receptor-ligand interaction in SCMC or by NaIO4 modification in ODCC may lead to the expression of cytotoxicity. The present studies demonstrate a functional role of surface carbohydrates on CTL in cell-to-cell recognition and interactions. Furthermore, the results suggest that target cell modification is not a requisite for recognition and lysis in an antigen-nonspecific cytotoxic system such as ODCC. However, partial blocking of ODCC by alloantibodies directed against the H-2 of unmodified target cells suggests that NaIO4-modified CTL recognize unrelated target H-2 antigens. The implication of these findings on the molecular mechanism of cell-mediated cytotoxicity is discussed.     

Effect of ligand density on the spectral, physical, and biological characteristics of CdSe/ZnS quantum dots

Chemical modification of the surface of CdSe/ZnS quantum dots (QDs) with small molecules or functional ligands often alters the characteristics of these particles. For instance, dopamine conjugation quenches the fluorescence of the QDs, which is a property that can be exploited for sensing applications if the conjugates are taken up into living cells. However, different sizes and/or preparations of mercaptocarboxylic acid solubilized QDs show very different properties when incubated with cells. It is unknown what physical parameters determine a QDs ability to interact with a cell surface, be endocytosed, escape from endosomes, and/or enter the nucleus. In this study, we examine the surface chemistry of QD-dopamine conjugates and present an optimized method for tracking the attachment of small biomolecules to the surface. It is found that the fluorescence intensity, surface charge, colloidal stability, and biological interactions of the QDs vary as a function of the density of dopamine on the surface. Successful targeting of QD-dopamine to dopamine receptor positive PC12 cells correlates with greater homogeneity of particle thiol layer, and a minimum number of ligands required for specific association can be estimated. These results will enable users to develop methods for screening QD conjugates for biological activity before proceeding to experiments with cell lines and animals.     

Effect of CdTe Quantum Dots Size on the Conformational Changes of Human Serum Albumin: Results of Spectroscopy and Isothermal Titration Calorimetry

Quantum dots (QDs) are recognized as some of the most promising candidates for future applications in biomedicine. However, concerns about their safety have delayed their widespread application. Human serum albumin (HSA) is the main protein component of the circulatory system. It is important to explore the interaction of QDs with HSA for the potential in vivo application of QDs. Herein, using spectroscopy and isothermal titration calorimetry (ITC), the effect of glutathione-capped CdTe quantum dots of different sizes on the HSA was investigated. After correction for the inner filter effect, the fluorescence emission spectra and synchronous fluorescence spectra showed that the microenvironment of aromatic acid residues in the protein was slightly changed when the glutathione (GSH)–cadmium telluride (CdTe) QDs was added, and GSH–CdTe QDs with larger particle size exhibited a much higher effect on HSA than the small particles. Although a ground-state complex between HSA and GSH–CdTe QDs was formed, the UV–vis absorption and circular dichroism spectroscopic results did not find appreciable conformational changes of HSA. ITC has been used for the first time to characterize the binding of QDs with HSA. The ITC results revealed that the binding was a thermodynamically spontaneous process mainly driven by hydrophobic interactions, and the binding constant tended to increase as the GSH–CdTe QDs size increased. These findings are helpful in understanding the bioactivities of QDs in vivo and can be used to assist in the design of biocompatible and stable QDs.     

The influence of elemental composition and surface topography on adhesion,proliferation and differentiation of osteoblasts

The influence of elemental composition and surface topography of substrates on the adhesion, proliferation and early differentiation stages of mouse osteoblasts, line MC3T3-E1, cultured on the surface of titanium and multicomponent bioactive nanostructured films (MuBiNaFs) Ti-Ca-(P)-C-O-N and Ti-Ca-Si-C-O-N has been studied. Osteoblasts spread both on the surface of uncoated titanium samples and on the samples coated with the films and had more elongated and irregular shape than the cells cultured on control glass substrate. Immunofluorescence study has shown that osteoblasts formed straight actin bundles associated with focal contacts. Osteoblasts on titanium films formed fewer focal contacts than the cells cultured on Ti-Ca-(P)-C-O-N films. The sandblast treatment did not affect the distribution of the focal contacts and actin structures within the cells. Osteoblasts actively divided on the surface of Ti-Ca-(P)-C-O-N and Ti-Ca-Si-C-O-N films and alteration of surface topography did not affect their growth rate. The quantitative colorimetrical test on alkaline phosphatase activity has shown that modification of surface topography does not affect the level of osteoblastic differentiation. Thus, the elemental composition plays an important role in the interaction of osteoblasts with the surface of films, while the modification of the surface topography in the range of S _q from 0.4 to 1 μm does not influence adhesion, proliferation, and differentiation of osteoblasts.     

Correlated light and electron microscopic imaging of multiple endogenous proteins using Quantum dots

The importance of locating proteins in their context within cells has been heightened recently by the accomplishments in molecular structure and systems biology. Although light microscopy (LM) has been extensively used for mapping protein localization, many studies require the additional resolution of the electron microscope. Here we report the application of small nanocrystals (Quantum dots; QDs) to specifically and efficiently label multiple distinct endogenous proteins. QDs are both fluorescent and electron dense, facilitating their use for correlated microscopic analysis. Furthermore, QDs can be discriminated optically by their emission wavelength and physically by size, making them invaluable for multilabeling analysis. We developed pre-embedding labeling criteria using QDs that allows optimization at the light level, before continuing with electron microscopy (EM). We provide examples of double and triple immunolabeling using light, electron and correlated microscopy in rat cells and mouse tissue. We conclude that QDs aid precise high-throughput determination of protein distribution.     

Long-term multiple color imaging of live cells using quantum dot bioconjugates

Luminescent quantum dots (QDs)--semiconductor nanocrystals--are a promising alternative to organic dyes for fluorescence-based applications. We have developed procedures for using QDs to label live cells and have demonstrated their use for long-term multicolor imaging of live cells. The two approaches presented are (i) endocytic uptake of QDs and (ii) selective labeling of cell surface proteins with QDs conjugated to antibodies. Live cells labeled using these approaches were used for long-term multicolor imaging. The cells remained stably labeled for over a week as they grew and developed. These approaches should permit the simultaneous study of multiple cells over long periods of time as they proceed through growth and development.     

Construction of photodynamic‐effect immunofluorescence probes by a complex of quantum dots,immunoglobulin G and chlorin e6 and their application in HepG2 cell killing

In this study, tri‐functional immunofluorescent probes (Ce6–IgG–QDs) based on covalent combinations of quantum dots (QDs), immunoglobulin G (IgG) and chlorin e6 (Ce6) were developed and their photodynamic ability to induce the death of cancer cells was demonstrated. Strategically, one type of second‐generation photosensitizer, Ce6, was first coupled with anti‐IgG antibody using the EDC/NHS cross‐linking method to construct the photosensitive immunoconjugate Ce6–IgG. Then, a complex of Ce6–IgG–QDs immunofluorescent probes was obtained in succession by covalently coupling Ce6–IgG to water soluble CdTe QDs. The as‐manufactured Ce6–IgG–QDs maintained the bio‐activities of both the antigen–antibody‐based tumour targeting effects of IgG and the photodynamic‐related anticancer activities of Ce6. By way of polyclonal antibody interaction with rabbit anti‐human epidermal growth factor receptor (anti‐EGFR antibody, N‐terminus), Ce6–IgG–QDs were labelled indirectly onto the surface of human hepatocarcinoma (HepG2) cells in cell recognition and killing experiments. The results indicated that the Ce6–IgG–QDs probes have excellent tumour cell selectivity and higher photosensitivity in photodynamic therapy (PDT) compared with Ce6 alone, due to their antibody‐based specific recognition and location of HepG2 cells and the photodynamic effects of Ce6 killed cells based on efficient fluorescence resonance energy transfer between QDs and Ce6. Copyright © 2015 John Wiley & Sons, Ltd.     

量子点细胞毒性及其作用机制

纳米粒子(NPS)在工业和研究中的使用急剧增加,因而这种材料面临一个其潜在毒性的问题。不幸的是,对纳米颗粒与纳米/生物界面可能发生的相互作用没有足够的了解。广大科技工作者正在积极寻求日益关注的纳米技术对人类的影响答案。我们将从NPS在生物媒体中的浓度,尺寸大小,电荷,和配位体的稳定性方面来了解纳米粒子的性质和他们在生物环境中对细胞毒所起的作用;并初步探讨已知的机制,量子点可以破坏细胞,包括氧化应激引起的活性氧(ROS)。微小浓度量子点足以造成长期持久的,甚至是跨代的影响。本文讨论了从纳摩尔到皮摩尔浓度的诱导细胞损伤的量子点(QDS)的浓度,这意味着含镉量子点可以发挥表观遗传毒性,纳米基因毒性,重金属基因的毒性。在此为评估包括量子点的在内的纳米毒性的的纳米材料,我们采用量子点作为一个例证,来阐述以科学为基础的发展到纳米毒理学的相关的问题。     

Bovine serum albumin functionalized blue emitting Ti3C2 MXene quantum dots as a sensitive fluorescence probe for Fe3+ ion detection and its toxicity analysis

In the present work, an improved class of protein functionalized fluorescent 2D Ti₃C₂ MXene quantum dots (MXene QDs) was prepared using a hydrothermal method. Exfoliated 2D Ti₃C₂ sheets were used as the starting precursor and transport protein bovine serum albumin (BSA) was used to functionalize the MXene QDs. BSA-functionalized MXene QDs exhibited excellent photophysical property and stability at various physiological parameters. High-resolution transmission electron microscopy analysis showed that the BSA@MXene QDs were quasispherical in shape with a size of ~2 nm. The fluorescence intensity of BSA@MXene QDs was selectively quenched in the presence of Fe³⁺ ions. The mechanism of fluorescence quenching was further substantiated using time-resolved fluorescence and Stern–Volmer analysis. The sensing assay showed a linear response within the concentration range 0–150 μM of Fe³⁺ ions with excellent limit of detection. BSA@MXene QDs probe showed good selectivity toward ferric ions even in the presence of other potential interferences. The practical applicability of BSA@MXene QDs was further tested in real samples for Fe³⁺ ion quantification and the sensor had good recovery rates. The cytotoxicity studies of the BSA@MXene QDs toward the human glioblastoma cells revealed that BSA@MXene QDs are biocompatible at lower doses and showed significant cytotoxicity at higher dosages.     

Maximizing specificity and yield of PCR by the quantum dot itself rather than property of the quantum dot surface

We found that semiconductor quantum dots (QDs) dramatically improved both product yield and specificity of PCR. The concentration of QDs is important for improving PCR amplification. In the presence of appropriate concentration of mercaptoacetic acid (MAA)-coated QDs, specificity and yield of PCR were enhanced. Also, strong nonspecific bands and weaker smeared bands were eliminated. At lower annealing temperatures (25–45 °C), addition of MAA-coated QDs into the PCR reagent produced specific PCR products without nonspecific sequence amplification. MAA alone did not improve PCR amplification. Streptavidin (SA) surface modified QDs with different size also effectively improved the specificity of PCR, demonstrating that the observed effect was not due to property of the QD surface but instead due to the QD itself. Bovine Serum Albumin (BSA) could relieve Taq polymerase from MAA-coated QDs in PCR by interaction with QDs and therefore imply that QDs improve specificity of PCR by interaction with Taq polymerase. These results demonstrate that QDs, added to reaction mixes at appropriate concentrations, can increase PCR yield and improve PCR specificity, even at low annealing temperatures. We assume that many different surface modified polymeric nanoparticles might have similar effects.     

Determination of a Threshold Dose to Reduce or Eliminate CdTe-Induced Toxicity in L929 Cells by Controlling the Exposure Dose

With the widespread use of quantum dots (QDs), the likelihood of exposure to quantum dots has increased substantially. The application of quantum dots in numerous biomedical areas requires detailed studies on their toxicity. In this study, we aimed to determine the threshold dose which reduced or eliminated CdTe-induced toxicity in L929 cells by controlling the exposure dose. We established a cellular model of acute exposure to CdTe QDs. Cells were exposed to different concentrations of CdTe QDs (2.2 nm and 3.5 nm) followed by illustrative cytotoxicity analysis. The results showed that low concentrations of CdTe QDs (under 10 µg/mL) promoted cell viability, caused no obvious effect on the rate of cell apoptosis, intracellular calcium levels and changes in mitochondrial membrane potential, while high concentrations significantly inhibited cell viability. In addition, reactive oxygen species in the 10 µg/mL-treated group was significantly reduced compared with the control group. In summary, the cytotoxicity of CdTe QDs on L929 cell is dose-dependent, time-dependent and size-dependent. Low concentrations of CdTe QDs (below 10 µg/mL) may be nontoxic and safe in L929 cells, whereas high concentrations (above 10 µg/mL) may be toxic resulting in inhibition of proliferation and induction of apoptosis in L929 cells.     

Controlled surface trap state photoluminescence from CdS QDs impregnated in poly(methyl methacrylate)

A method of microwave (MW) assisted synthesis was employed to prepare cadmium sulfide (CdS) quantum dots (QDs) in dimethylformamide in the presence of poly(methyl methacrylate) (PMMA). The MW irradiation was carried out for a fixed time of 20-30 s and the size of QDs varied from 2.9-5.5 nm. Before each irradiation the solution was cooled down to ambient temperature and the irradiation process was repeated six times. An increase in the intensity and red shift of the characteristic UV-vis absorption peak originating from CdS QDs were observed with repeated MW irradiation, suggesting that the amount of generated CdS QDs increased within the PMMA network and aggregated with repeated MW irradiation. MW irradiation could influence selectively the nucleation and growing rates of PMMA-CdS QDs systems. The broadness and large Stokes shift of the emission from Cd(2+)-rich PMMA-CdS QDs was due to the surface trap state photoluminescence. The recombination of shallow trapped electrons and shallow trapped holes has been considered as the primary source of the surface trap state photoluminescence in Cd(2+)-rich PMMA-CdS QDs. The photoluminescence lifetime was observed to be decreased sharply when the amount of QDs was less, showing the emission decay was dependent on the surface property of PMMA-CdS QDs. The origin of the longer lifetime was due to the involvement of surface trap states and dependent on the amount of CdS QDs present within PMMA and its environment. The effect of the concentration of Cd(2+), S(2-) and PMMA on the generation of CdS QDs within PMMA and the effect of repeated MW irradiation on the optical properties was studied and the results are discussed in this article.     

Fluorescence intensity modulation of CdSe/ZnS quantum dots assesses reactive oxygen species during chemotherapy and radiotherapy for cancer cells

Quantum dots (QDs) are semiconductor nanoparticles ranging in size from 2 to 10 nm. QDs are increasingly being developed for biomedical imaging, targeted drug delivery and green energy technology. These have led to much research on QD interactions with various physical, chemical and biological systems. For biological systems, research has focused on the biocompatibility/cytotoxicity of QDs in the context of imaging/therapy. However, there is a paucity of work on how biological systems and bioactive molecules might be used to alter the optoelectronic properties of QDs. Here, it is shown that these properties can be altered by reactive oxygen species (ROS) from chemotherapeutic media and biological cells following controlled changes in cellular activities. Using CdSe/ZnS core‐shell QDs, spectroscopic analysis of optically excited QDs with HL60, K562 and T98G cancer cell lines is performed. Our results show statistically significant (P < 0.0001) modulation of the fluorescence emission spectra of the QDs due to the ROS produced by common chemotherapeutic drugs, daunorubicin and doxorubicin and by cells following chemotherapy/radiotherapy. This optical modulation, in addition to assessing ROS generation, will possibly enhance applications of QDs in simultaneous diagnostic imaging and nanoparticle‐mediated drug delivery as well as simultaneous ROS assessment and radiosensitization for improved outcomes in cancer treatments. Reactive molecular species produced by biological cells and chemotherapeutic drugs can create electric fields that alter the photophysical properties of QDs, and this can be used for concurrent monitoring of cellular activities, while inducing changes in those cellular activities.      

Quantifying engineered nanomaterial toxicity: comparison of common cytotoxicity and gene expression measurements

Background

When evaluating the toxicity of engineered nanomaterials (ENMS) it is important to use multiple bioassays based on different mechanisms of action. In this regard we evaluated the use of gene expression and common cytotoxicity measurements using as test materials, two selected nanoparticles with known differences in toxicity, 5 nm mercaptoundecanoic acid (MUA)-capped InP and CdSe quantum dots (QDs). We tested the effects of these QDs at concentrations ranging from 0.5 to 160 µg/mL on cultured normal human bronchial epithelial (NHBE) cells using four common cytotoxicity assays: the dichlorofluorescein assay for reactive oxygen species (ROS), the lactate dehydrogenase assay for membrane viability (LDH), the mitochondrial dehydrogenase assay for mitochondrial function, and the Comet assay for DNA strand breaks.

Results

The cytotoxicity assays showed similar trends when exposed to nanoparticles for 24 h at 80 µg/mL with a threefold increase in ROS with exposure to CdSe QDs compared to an insignificant change in ROS levels after exposure to InP QDs, a twofold increase in the LDH necrosis assay in NHBE cells with exposure to CdSe QDs compared to a 50% decrease for InP QDs, a 60% decrease in the mitochondrial function assay upon exposure to CdSe QDs compared to a minimal increase in the case of InP and significant DNA strand breaks after exposure to CdSe QDs compared to no significant DNA strand breaks with InP. High-throughput quantitative real-time polymerase chain reaction (qRT-PCR) data for cells exposed for 6 h at a concentration of 80 µg/mL were consistent with the cytotoxicity assays showing major differences in DNA damage, DNA repair and mitochondrial function gene regulatory responses to the CdSe and InP QDs. The BRCA2, CYP1A1, CYP1B1, CDK1, SFN and VEGFA genes were observed to be upregulated specifically from increased CdSe exposure and suggests their possible utility as biomarkers for toxicity.

Conclusions

This study can serve as a model for comparing traditional cytotoxicity assays and gene expression measurements and to determine candidate biomarkers for assessing the biocompatibility of ENMs.

     

Involvement of ABC transporters in the efflux and toxicity of MPA‐COOH‐CdTe quantum dots in human breast cancer SK‐BR‐3 cells

This paper aimed to study the possible involvement of adenosine triphosphate‐binding cassette (ABC) transporters in the detoxification of quantum dots (QDs) in human breast carcinoma (SK‐BR‐3) cells. The effects of QD sizes on such interactions were also evaluated. For this purpose, we used monodispersed MPA‐COOH‐CdTe QDs with different diameters (emission length at 560 and 625 nm, named as QD‐560 and QD‐625). Such QDs tended to accumulate in cells and cause significant toxicity. Using specific inhibitors of ABC transporters, the cellular accumulation and toxicity of QDs in SK‐BR‐3 cells were significantly affected. Moreover, treatment of QDs caused concentration‐ and time‐dependent induction of ABC transporters. Furthermore, the induction effects of smaller QDs were found to be greater than larger ones at equivalent concentrations, suggesting a size‐dependent recognition of substrates by ABC transporters. Overall, these results provided important support for the modulation of QDs toxicity by ABC transporters.