Impact of Surface Ligand on the Biocompatibility of InP/ZnS Quantum Dots with Platelets.

InP/ZnS quantum dots (QDs) have received a large focus in recent years as a safer alternative to heavy metal-based QDs. Given their intrinsic fluorescent imaging capabilities, these QDs can be potentially relevant for in vivo platelet imaging. The InP/ZnS QDs are synthesized and their biocompatibility investigated through the use of different phase transfer agents. Analysis of platelet function indicates that platelet-QD interaction can occur at all concentrations and for all QD permutations tested. However, as the QD concentration increases, platelet aggregation is induced by QDs alone independent of natural platelet agonists. This study helps to define a range of concentrations and coatings (thioglycolic acid and penicillamine) that are biocompatible with platelet function. With this information, the platelet-QD interaction can be identified using multiple methods. Fluorescent lifetime imaging microscopy (FLIM) and confocal studies have shown QDs localize on the surface of the platelet toward the center while showing evidence of energy transfer within the QD population. It is believed that these findings are an important stepping point for the development of fluorescent probes for platelet imaging.

Influence of InP/ZnS Quantum Dots on Thermodynamic Properties and Morphology of the DPPC/DPPG Monolayers at Different Temperatures.

In this work, the effects of InP/ZnS quantum dots modified with amino or carboxyl group on the characteristic parameters in phase behavior, elastic modulus, relaxation time of the DPPC/DPPG mixed monolayers are studied by the Langmuir technology at the temperature of 37, 40 and 45 °C. Additionally, the information on the morphology and height of monolayers are obtained by the Langmuir-Bloggett technique and atomic force microscope technique. The results suggest that the modification of the groups can reduce the compressibility of monolayers at a higher temperature, and the most significant effect is the role of the amino group. At a high temperature of 45 °C, the penetration ability of InP/ZnS-NH2 quantum dots in the LC phase of the mixed monolayer is stronger. At 37 °C and 40 °C, there is no clear difference between the penetration ability of InP/ZnS-NH2 quantum dots and InP/ZnS-COOH quantum dots. The InP/ZnS-NH2 quantum dots can prolong the recombination of monolayers at 45 °C and accelerate it at 37 °C and 40 °C either in the LE phase or in the LC phase. However, the InP/ZnS-COOH quantum dots can accelerate it in the LE phase at all temperatures involved but only prolong it at 45 °C in the LC phase. This work provides support for understanding the effects of InP/ZnS nanoparticles on the structure and properties of cell membranes, which is useful for understanding the behavior about the ingestion of nanoparticles by cells and the cause of toxicity.

Synergistic Effect of Halogen Ions and Shelling Temperature on Anion Exchange Induced Interfacial Restructuring for Highly Efficient Blue Emissive InP/ZnS Quantum Dots.

InP quantum dots (QDs) have attracted much attention owing to their nontoxic properties and shown great potential in optoelectronic applications. Due to the surface defects and lattice mismatch, the interfacial structure of InP/ZnS QDs plays a significant role in their performance. Herein, the formation of In-S and Sx -In-P1-x interlayers through anion exchange at the shell-growth stage is revealed. More importantly, it is proposed that the composition of interface is dependent on the synergistic effect of halogen ions and shelling temperature. High shelling temperature contributes to the optical performance improvement resulting from the formation of interlayers, besides the thicker ZnS shell. Moreover, the effect relates to the halogen ions where I- presents more obvious enhancement than Br- and Cl- , owing to their different ability to coordinate with In dangling bonds, which are inclined to form In-S and Sx -In-P1-x bonds. Further, the anion exchange under I- -rich environment causes a blue-shift of emission wavelength with shelling temperature increasing, unobserved in a Cl- - or Br- -rich environment. It contributes to the preparation of highly efficient blue emissive InP/ZnS QDs with emission wavelength of 473 nm, photoluminescence quantum yield of ≈50% and full width at half maximum of 47 nm.

Nephrotoxicity Evaluation of Indium Phosphide Quantum Dots with Different Surface Modifications in BALB/c Mice.

InP QDs have shown a great potential as cadmium-free QDs alternatives in biomedical applications. It is essential to understand the biological fate and toxicity of InP QDs. In this study, we investigated the in vivo renal toxicity of InP/ZnS QDs terminated with different functional groups-hydroxyl (hQDs), amino (aQDs) and carboxyl (cQDs). After a single intravenous injection into BALB/c mice, blood biochemistry, QDs distribution, histopathology, inflammatory response, oxidative stress and apoptosis genes were evaluated at different predetermined times. The results showed fluorescent signals from QDs could be detected in kidneys during the observation period. No obvious changes were observed in histopathological detection or biochemistry parameters. Inflammatory response and oxidative stress were found in the renal tissues of mice exposed to the three kinds of QDs. A significant increase of KIM-1 expression was observed in hQDs and aQDs groups, suggesting hQDs and aQDs could cause renal involvement. Apoptosis-related genes (Bax, Caspase 3, 7 and 9) were up-regulated in hQDs and aQDs groups. The above results suggested InP/ZnS QDs with different surface chemical properties would cause different biological behaviors and molecular actions in vivo. The surface chemical properties of QDs should be fully considered in the design of InP/ZnS QDs for biomedical applications.

A study on the mechanism of Indium phosphide/zinc sulfide core/shell quantum dots influencing embryo incubation of rare minnow (Gobiocypris rarus).

Quantum dots (QDs) inhibit fish hatching, but the mechanism is still unclear. In this study, the effect of Indium phosphide/zinc sulfide quantum dots (InP/ZnS QDs) on the embryo incubation of rare minnow was investigated. Five experimental concentration groups were set up according to the preliminary experimental results, which were 0, 50, 100, 200 and 400 nM. A direct exposure method was adopted to expose embryos to InP/ZnS QDs solution. The results showed that InP/ZnS QDs significantly inhibited the embryo hatching rate, delayed embryo emergence, affected the expression of genes associated with hatching gland cells and hatching enzymes. InP/ZnS QDs also destroy the structure of the embryo chorion. In addition, QDs can cause oxidative stress in embryos. Transcriptional sequencing analysis showed that InP/ZnS QDs InP/ZnS QDs may have induced the production of a hypoxic environment and triggered induce abnormal cardiac muscle contraction, inflammatory response and apoptosis process in embryos. In conclusion, QDs influences embryo hatchability largely through egg chorion mediation.

InP/ZnS quantum dots cause liver damage in rare minnow (Gobiocypris rarus) larvae.

InP/ZnS quantum dots (QDs) are widely used in biomedical imaging and light-emitting component manufacturing industries, but there are few studies on their biological toxicity. In this study, we conducted experiments with rare minnow larvae and found that InP/ZnS QDs can cause liver damage. InP/ZnS QDs appeared only in the intestine of larvae and were not enriched in other parts of the larvae. The activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (AKP) increased, while the decrease in bile acid. InP/ZnS QDs caused hepatic cell nuclear lysis, abnormal cytoplasmic staining, and mitochondrial cristae reduction, swelling, and fragmentation. RNA-sequencing results revealed that InP/ZnS QDs exposure treatment affected the expression of genes involved in lipid metabolism, sterol synthesis, bile acid synthesis and other pathways. The excessive production of reactive oxygen species (ROS) induced by InP/ZnS QDs may be the main source of toxicity.

Intelligent multicolor nano-sensor based on nontoxic dual fluoroprobe and MOFs for colorful consecutive detection of Hg2+ and cysteine.

Ultrasensitive detection of Hg2+ in aquatic ecosystems is of great significance due to its high toxicity and ubiquity in water. Herein, using a one-step in-situ synthesis method, blue fluorescent carbon dots (CDs), red fluorescent InP/ZnS quantum dots (InPQDs), and MOFs (ZIF-8) integrated multicolor nano-sensor CDs/InPQDs@ZIF-8 was constructed for consecutive visual detection of Hg2+ and Cys. The InPQDs can act as the response unit for Hg2+ and Cys, with the limit of detection (LOD) of 8.68 and 37.96 nM, respectively. Significantly, the low detection limit combines with good specificity and accuracy of the nano-sensor meet the requirement for the safety monitoring and control of Hg2+ in drinking and environmental water. Moreover, the color recognition and processing software installed on smart phone can realize the real-time and rapid sensing of Hg2+ and Cys. A logic gate circuit was also devised, providing the possibilities for the application of the nano-sensor in the field of intelligent devices. As far as we know, this was the first example to apply InPQDs to the continuous multicolor visual detection of Hg2+ and Cys, which provided reference for the construction of environmentally-friendly dual emission fluorescent sensors for hazardous substance monitoring.

Reproductive toxicity of InP/ZnS QDs in male rare minnow (Gobiocypris rarus).

InP/ZnS quantum dots (QDs) stand out among cadmium-free alternatives for higher exciton Bohr radius and strong quantum confined effect. In this study, the reproductive toxicity and mechanism of InP/ZnS QDs at different concentrations in male Chinese rare minnows (Gobiocypris rarus) were investigated. The results showed that QDs in 800 nmol/L concentration group could enter the testes after 1 d of exposure and caused changes in the structure of the testes, including the scattered distribution of seminal vesicles, reduction in germ cells and vacuolation in some areas of interstitial cells. The expression levels of androgen receptor (Ar) and doublesex and mab-3 related transcription factor 1 (Dmrt1) and the tight junction protein-related genes ß-catenin and occludin were upregulated in rare minnows. The sperm quality and ATP content of parents in the 800 nmol/L treatment group were significantly decreased. Continuous detection of the development of F1 generation embryos showed that parental exposure to InP/ZnS QDs reduced the heart rate and spontaneous movement frequency of F1 generation embryos, and the fertilization rate of the F1 generation in the 800 nmol/L treatment group was significantly reduced. In general, the sperm quality and testicular structure of adult rare minnows were not significantly affected by concentrations below 400 nmol/L. High-concentration InP/ZnS QDs exposure can damage the integrity of the blood-testis barrier (BTB) and cause reproductive damage to the parents of rare minnows, which will continue to the next generation and affect their development.

Ambipolar Charge Storage in Type-I Core/Shell Semiconductor Quantum Dots toward Optoelectronic Transistor-Based Memories.

Efficient charge storage media play a pivotal role in transistor-based memories and thus are under intense research. In this work, the charge storage ability of type-I InP/ZnS core/shell quantum dots is well revealed through studying a pentacene-based organic transistor with the quantum dots (QDs) integrated. The quantum well-like energy band structure enables the QDs to directly confine either holes or electrons in the core, signifying a dielectric layer-free nonvolatile memory. Especially, the QDs in this device can be charged by electrons using light illumination as the exclusive method. The electron charging process is ascribed to the photoexcitation process in the InP-core and the hot holes induced. The QDs layer demonstrates an electron storage density of ≈5.0 × 1011  cm-2 and a hole storage density of ≈6.4 × 1011  cm-2 . Resultingly, the output device shows a fast response speed to gate voltage (10 µs), large memory window (42 V), good retention (>4.0 × 104 s), and reliable endurance. This work suggests that the core/shell quantum dot as a kind of charge storage medium is of great promise for optoelectronic memories.

In vivo Comparison of the Biodistribution and Toxicity of InP/ZnS Quantum Dots with Different Surface Modifications.

INTRODUCTION: Indium phosphide (InP) quantum dots (QDs) have shown a broad application prospect in the fields of biophotonics and nanomedicine. However, the potential toxicity of InP QDs has not been systematically evaluated. In particular, the effects of different surface modifications on the biodistribution and toxicity of InP QDs are still unknown, which hinders their further developments. The present study aims to investigate the biodistribution and in vivo toxicity of InP/ZnS QDs. METHODS: Three kinds of InP/ZnS QDs with different surface modifications, hQDs (QDs-OH), aQDs (QDs-NH2), and cQDs (QDs-COOH) were intravenously injected into BALB/c mice at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively. Biodistribution of three QDs was determined through cryosection fluorescence microscopy and ICP-MS analysis. The subsequent effects of InP/ZnS QDs on histopathology, hematology and blood biochemistry were evaluated at 1, 3, 7, 14 and 28 days post-injection. RESULTS: These types of InP/ZnS QDs were rapidly distributed in the major organs of mice, mainly in the liver and spleen, and lasted for 28 days. No abnormal behavior, weight change or organ index were observed during the whole observation period, except that 2 mice died on Day 1 after 25 mg/kg BW hQDs treatment. The results of H&E staining showed that no obvious histopathological abnormalities were observed in the main organs (including heart, liver, spleen, lung, kidney, and brain) of all mice injected with different surface-functionalized QDs. Low concentration exposure of three QDs hardly caused obvious toxicity, while high concentration exposure of the three QDs could cause some changes in hematological parameters or biochemical parameters related to liver function or cardiac function. More attention needs to be paid on cQDs as high-dose exposure of cQDs induced death, acute inflammatory reaction and slight changes in liver function in mice. CONCLUSION: The surface modification and exposure dose can influence the biological behavior and in vivo toxicity of QDs. The surface chemistry should be fully considered in the design of InP-based QDs for their biomedical applications.

Cytotoxicity of InP/ZnS Quantum Dots With Different Surface Functional Groups Toward Two Lung-Derived Cell Lines.

Although InP/ZnS quantum dots (QDs) have emerged as a presumably less hazardous alternative to cadmium-based QDs, their toxicity has not been fully understood. In this work, we report the cytotoxicity of InP/ZnS QDs with different surface groups (NH2, COOH, OH) toward two lung-derived cell lines. The diameter and the spectra of InP/ZnS QDs were characterized and the hydrodynamic size of QDs in aqueous solution was compared. The confocal laser scanning microscopy was applied to visualize the labeling of QDs for human lung cancer cell HCC-15 and Alveolar type II epithelial cell RLE-6TN. The flow cytometry was used to confirm qualitatively the uptake efficiency of QDs, the cell apoptosis and ROS generation, respectively. The results showed that in deionized water, InP/ZnS-OH QDs were easier to aggregate, and the hydrodynamic size was much greater than the other InP/ZnS QDs. All these InP/ZnS QDs were able to enter the cells, with higher uptake efficiency for InP/ZnS-COOH and InP/ZnS-NH2 at low concentration. High doses of InP/ZnS QDs caused the cell viability to decrease, and InP/ZnS-COOH QDs and InP/ZnS-NH2 QDs appeared to be more toxic than InP/ZnS-OH QDs. In addition, all these InP/ZnS QDs promoted cell apoptosis and intracellular ROS generation after co-cultured with cells. These results suggested that appropriate concentration and surface functional groups should be optimized when InP/ZnS QDs are utilized for biological imaging and therapeutic purpose in the future.

Doxorubicin-conjugated D-glucosamine- and folate- bi-functionalised InP/ZnS quantum dots for cancer cells imaging and therapy.

Nanoscaled quantum dots (QDs), with unique optical properties have been used for the development of theranostics. Here, InP/ZnS QDs were synthesised and functionalised with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalised QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In:MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11 nm). Energy-dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs. MTT analysis in the OVCAR-3 cells treated with bare QDs, QD-FA, QD-GA, QD-FA-GA and QD-FA-GA-DOX (0.2 mg/mL of QDs) after 24 h indicated low toxicity for the bare QDs and functionalised QDs (about 80-90% cell viability). QD-FA-GA-DOX nanoparticles elicited toxicity in the cells. Cellular uptake of the engineered QDs were investigated in both folate receptor (FR)-positive OVCAR-3 cells and FR-negative A549 cells using fluorescence microscopy and FACS flow cytometry. The FA-functionalised QDs showed significantly higher uptake in the FR-positive OVCAR-3 cells, nonetheless the GA-functionalised QDs resulted in an indiscriminate uptake in both cell lines. In conclusion, our findings indicated that DOX-conjugated FA-armed QDs can be used as theranostics for simultaneous imaging and therapy of cancer.

InP/ZnS QDs exposure induces developmental toxicity in rare minnow (Gobiocypris rarus) embryos.

We investigated the in vivo toxicity of InP/ZnS quantum dots (QDs) in Chinese rare minnow (Gobiocypris rarus) embryos. The 72 h post-fertilization (hpf) LC50 (median lethal concentration) was 1678.007 nmol/L. Rare minnows exposed to InP/ZnS QDs exhibited decreased spontaneous movement, decreased survival and hatchability rates, and an increased malformation rate. Pericardial edema, spinal curvature, bent tails and vitelline cysts were observed. Embryonic Wnt8a and Mstn mRNA levels were significantly up-regulated after InP/ZnS QDs treatment at 48 hpf (200 nmol/L) (p < 0.05). The superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels at 96 hpf (800 nmol/L) had an increasing trend. Hsp70 mRNA expression was significantly changed at 48 hpf (200 nmol/L), but compared with the blank control, the different InP/ZnS QDs treatments did not significantly change the Olive tail moments (p > 0.05). Thus, InP/ZnS QDs caused teratogenic effects and death during the development of Chinese rare minnow embryos, but InP/ZnS QDs did not cause significant genetic toxicity during Chinese rare minnow development.

Systematical investigation of in vitro interaction of InP/ZnS quantum dots with human serum albumin by multispectroscopic approach.

Cadmium-free quantum dots (QDs) have attracted great attention in biological and biomedical applications due to their less content of toxic metals, but their potential toxicity investigations on molecular biology level are rarely involved. Since few studies have addressed whether InP/ZnS QDs could bind and alter the structure and function of human serum albumin (HSA), in vitro interaction between InP/ZnS QDs and HSA was systematically characterized by multispectroscopic approaches. InP/ZnS QDs could quench the intrinsic fluorescence of HSA via static mode. The binding site of InP/ZnS QDs was mainly located at subdomain IIA of HSA. Some thermodynamic parameters suggested that InP/ZnS QDs interacted with HSA mainly through electrostatic interactions. As further revealed by three-dimensional spectrometry, FT-IR spectrometry and circular dichroism technique, InP/ZnS QDs caused more global and local conformational change of HSA than CdSe/ZnS QDs, which illustrated the stronger binding interaction and higher potential toxicity of InP/ZnS QDs on biological function of HSA. Our results offer insights into the in vitro binding mechanism of InP/ZnS QDs with HSA and provide important information for possible toxicity risk of these cadmium-free QDs to human health.