Search

Hypothesis: Trypanosomiasis is one of the main threats to human and animal health in African countries. Trypanosoma brucei can evade the host immune recognition by rapidly altering its variant surface glycoprotein (VSG). The ATP synthase F 1 subunit of the parasite exhibits extremely low similarity to that of its mammalian hosts, hypothetically making it an ideal target for the development of novel therapeutics., Experiments: Graphene quantum dots (GQDs) were synthesized, and their adhesion to T. brucei surface and internalization was observed microscopically. The activity of ATP synthase and mitochondrial membrane potential of T. brucei were measured after exposure to GQDs. Proteomics, biolayer interferometry, and molecular dynamic simulations were utilized to evaluate the interaction between GQDs with the target proteins., Findings: GQDs specifically adhered to the VSG of T. brucei and were conveyed inside the parasite via the VSG internalization pathway. The GQDs promoted intracellular ROS production, interacted with, and inhibited the activity of the p18 subunit of ATP synthase, disrupted parasite mitochondrial membrane potential. Additionally, the GQDs caused a decrease in aminoacyl - tRNA biosynthesis, and upregulated RNA and protein degradation pathways. The findings of this study offer a novel avenue for the target-oriented discovery of anti-trypanosome drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Salt stress has strongly impacted the long-term growth of eco-friendly farming worldwide. By targeting the oxidative stress induced by salt, the utilization of biomass-derived carbon dots (CDs) that possess high-efficiency antioxidant properties, are nontoxic, and have excellent biocompatibility represents a viable and effective approach for enhancing the salt tolerance of plants. In this study, we blended magnesium oxide nanoparticles with carbon sources derived from durian shells to construct Mg-doped carbon dots (Mg-CDs) through a hydrothermal reaction. We demonstrated that the foliar application of 150 μg/mL Mg-CDs to rice plants after treatment with 100 mM salt effectively increased the plant height (9.52%), fresh weight (22.41%), dry weight (33.33%), K + content (21.46%), chlorophyll content (36.21%), and carotenoid content (16.21%); decreased the malondialdehyde (MDA) (9.43%), Na + (25.75%), H 2 O 2 (17.50%), and O 2 •- contents (37.99%); and promoted the photosynthetic system and antioxidant activity. Transcriptome analysis revealed that Mg-CD pretreatment triggered transcriptional reprogramming in rice seedlings. The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes pathways based on trend groups of gene expression patterns of Profile 8 and Profile 15 indicated that priming with Mg-CDs activated stress signaling- and defense-related pathways, such as metabolic pathways, biosynthesis of secondary metabolites, and photosynthesis pathways. These activations subsequently prompted the expression of genes related to the mitogen-activated protein kinase signaling pathway, hormone signal transduction, the oxidative stress response, and the photosynthetic system. This study demonstrated that the use of Mg-CDs represents a potential strategy to increase plant salt tolerance, creating the possibility for the regulation of crop salinity stress and offering valuable advancements in sustainable agriculture.

Mitochondria transplantation has emerged as a successful therapeutic modality to treat several degenerative diseases. However, the biodistribution of transplanted mitochondria has not been well studied. We investigated the ex-vivo systemic biodistribution and therapeutic efficacy of intravenously transplanted graphene quantum dots (GQDs) conjugated to isolated mitochondria (Mt-GQDs) in diabetic rat tissues. The results revealed that Mt-GQDs facilitate the tracking of transplanted mitochondria without affecting their therapeutic efficacy. It is compelling to note that Mt-GQDs and isolated mitochondria show comparable therapeutic efficacies in decreasing blood glucose levels, oxidative stress, inflammatory gene expressions, and restoration of different mitochondrial functions in pancreatic tissues of diabetic rats. In addition, histological section examination under a fluorescence microscope demonstrated the localization of Mt-GQDs in multiple tissues of diabetic rats. In conclusion, this study indicates that Mt-GQDs provide an effective mitochondrial transplantation tracking modality., Competing Interests: Declarations. Consent for Publication: The corresponding author on behalf of all the authors authorizes the publishers to publish the data after acceptance. Consent to Participate: Not Applicable. Ethics Declaration Statement: The approval for animal work was received from the Institutional Animal Ethics Committee (BV/IAEC/74/2021) at Banasthali Vidyapith, Rajasthan, India-304022. Competing Interests: The authors declare no competing interests., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Evolvulus alsinoides, a therapeutically valuable shrub can provide consistent supply of secondary metabolites (SM) with pharmaceutical significance. Nonetheless, because of its short life cycle, fresh plant material for research and medicinal diagnostics is severely scarce throughout the year. The effects of exogenous carbon quantum dot (CD) application on metabolic profiles, machine learning (ML) prediction of metabolic stress response, and SM yields in hairy root cultures of E. alsinoides were investigated and quantified. The range of the particle size distribution of the CDs was between 3 and 7 nm. The CDs EPR signal and spin trapping experiments demonstrated the formation of O2 -• spin-adducts at (g = 2.0023). Carbon dot treatment increased the levels of hydrogen peroxide and malondialdehyde concentrations as well as increased antioxidant enzyme activity. CD treatments (6 μg mL-1) significantly enhanced the accumulation of squalene and stigmasterol (7 and 5-fold respectively). The multilayer perceptron (MLP) algorithm demonstrated remarkable prediction accuracy (MSE value = 1.99E-03 and R2 = 0.99939) in both the training and testing sets for modelling. Based on the prediction, the maximum oxidative stress index and enzymatic activities were highest in the medium supplemented with 10 μg mL-1 CDs. The outcome of this study indicated that, for the first time, using CD could serve as a novel elicitor for the production of valuable SM. MLP may also be used as a forward-thinking tool to optimize and predict SM with high pharmaceutical significance. This study would be a touchstone for understanding the use of ML and luminescent nanomaterials in the production and commercialization of important SM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

After entering host cells by endocytosis, influenza A virus (IAV) is transported along microfilaments and then transported by dynein along microtubules (MTs) to the perinuclear region for genome release. Understanding the mechanisms of dynein-driven transport is significant for a comprehensive understanding of IAV infection. In this work, the roles of dynactin in dynein-driven transport of IAV were quantitatively dissected in situ using quantum dot-based single-virus tracking. It was revealed that dynactin was essential for dynein to transport IAV toward the nucleus. After virus entry, virus-carrying vesicles bound to dynein and dynactin before being delivered to MTs. The attachment of dynein to the vesicles was dependent on dynactin and its subunits, p150 Glued and Arp1. Once viruses reached MTs, dynactin-assisted dynein initiates retrograde transport of IAV. Importantly, the retrograde transport of viruses could be initiated at both plus ends (32%) and other regions on MTs (68%). Subsequently, dynactin accompanied and assisted dynein to persistently transport the virus along MTs in the retrograde direction. This study revealed the dynactin-dependent dynein-driven transport process of IAV, enhancing our understanding of IAV infection and providing important insights into the cell's endocytic transport mechanism.

The enormous potential of carbon dots (CDs) in agriculture has been widely reported, whereas their accurate distribution, transformation, and metabolic fate and potential soil health effects are not clearly understood. Herein, 13 C-labeled CDs ( 13 C-CDs) were sprayed on maize leaf, accumulated in all tissues, and promoted photosynthesis. Specifically, 13 C-CDs were internalized to participate in the synthesis of glucose, sucrose, citric acid, glyoxylate, and chlorogenic acid, promoting tricarboxylic acid cycle (TCA) and phenylalanine metabolism. Additionally, the catabolism of 13 C-CDs in vivo was mainly mediated by O 2 •- produced by oxidative stress. 13 C-CDs did not have an obvious impact on the soil environment at the overall level. The detection of 13 C signals in soil fauna suggested 13 C-CDs in soil food chain transmission. This study systematically described the exact fate of CDs in plants and potential soil ecological risks and provided a more comprehensive analysis and support for the potential advantages of CDs in agricultural application.

Efficient delivery of nanoparticles (NPs) to plants is important for agricultural application. However, to date, we still lack knowledge about how NPs' charge matters for its translocation pathway, i.e., symplastic and apoplastic pathways, in plants. In this study, we synthesized and used negatively charged citrate sourced carbon dots (C-CDs, -37.97 ± 1.89 mV), Cy5 coated C-CDs (Cy5-C-CDs, -41.90 ± 2.55 mV), positively charged PEI coated carbon dots (P-CDs, +43.03 ± 1.71 mV), and Cy5 coated P-CDs (Cy5-P-CDs, +48.80 ± 1.21 mV) to investigate the role of surface charges and coatings on the employed translocation pathways (symplastic and apoplastic pathways) of charged NPs in plants. Our results showed that, different from the higher fluorescence intensity of P-CDs and Cy5-P-CDs in extracellular than intracellular space, the fluorescence intensity of C-CDs and Cy5-C-CDs was similar between intracellular and extracellular space in cucumber and cotton roots. It suggests that the negatively charged CDs were translocated via both symplastic and apoplastic pathways, but the positively charged CDs were mainly translocated via the apoplastic pathway. Furthermore, our results showed that root applied negatively charged C-CDs demonstrated higher leaf fluorescence than did positively charged P-CDs in both cucumber (8.09 ± 0.99 vs 3.75 ± 0.23) and cotton (7.27 ± 1.06 vs 3.23 ± 0.22), indicating that negatively charged CDs have a higher translocation efficiency from root to leaf than do positively charged CDs. It should be noted that CDs do not affect root cell activities, ROS level, and photosynthetic performance in cucumber and cotton, showing its good biocompatibility. Overall, this study not only figured out that root applied negatively charged CDs employed both symplastic and apoplastic pathways to do the transportation in roots compared with mainly the employment of apoplastic pathway for positively charge CDs, but also found that negatively charge CDs could be more efficiently translocated from root to leaf than positively charged CDs, indicating that imparting negative charge to NPs, at least CDs, matters for its efficient delivery in crops.

The nuclear pore complexes on the nuclear membrane serve as the exclusive gateway for communication between the nucleus and the cytoplasm, regulating the transport of various molecules, including nucleic acids and proteins. The present work investigates the kinetics of the transport of negatively charged graphene quantum dots through nuclear membranes, focusing on quantifying their transport characteristics. Experiments are carried out in permeabilized HeLa cells using time-lapse confocal fluorescence microscopy. Our findings indicate that negatively charged graphene quantum dots exhibit rapid transport to the nuclei, involving two distinct transport pathways in the translocation process. Complementary experiments on the nuclear import and export of graphene quantum dots validate the bi-directionality of transport, as evidenced by comparable transport rates. The study also shows that the negatively charged graphene quantum dots possess favorable retention properties, underscoring their potential as drug carriers., (© 2024. The Author(s).)

Quantum dots (QDs) are semiconductor nanocrystals (2-10 nm) with unique optical and electronic properties due to quantum confinement effects. They offer high photostability, narrow emission spectra, broad absorption spectrum, and high quantum yields, making them versatile in various applications. Due to their highly reactive surfaces, QDs can conjugate with biomolecules while being used, produced, or unintentionally released into the environment. This systematic review delves into intricate relationship between QDs and proteins, examining their interactions that influence their physicochemical properties, enzymatic activity, ligand binding affinity, and stability. The research utilized electronic databases like PubMed, WOS, and Proquest, along with manual reviews from 2013 to 2023 using relevant keywords, to identify suitable literature. After screening titles and abstracts, only articles meeting inclusion criteria were selected for full text readings. This systematic review of 395 articles identifies 125 articles meeting the inclusion criteria, categorized into five overarching themes, encompassing various mechanisms of QDs and proteins interactions, including adsorption to covalent binding, contingent on physicochemical properties of QDs. Through a meticulous analysis of existing literature, it unravels intricate nature of interaction, significant influence on nanomaterials and biological entities, and potential for synergistic applications harnessing both specific and nonspecific interactions across various fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Liquid‒liquid phase separation (LLPS) is a ubiquitous process in which proteins, RNA, and biomolecules assemble into membrane-less compartments, playing important roles in many biological functions and diseases. The current knowledge on the biophysical and biochemical principles of LLPS is largely from in vitro studies; however, the physiological environment in living cells is complex and not at equilibrium. The characteristics of intracellular dynamics and their roles in physiological LLPS remain to be resolved. Here, by using single-particle tracking of quantum dots and dynamic monitoring of the formation of stress granules (SGs) in single cells, the spatiotemporal dynamics of intracellular transport in cells undergoing LLPS are quantified. It is shown that intracellular diffusion and active transport are both reduced. Furthermore, the formation of SG droplets contributes to increased spatial heterogeneity within the cell. More importantly, the study demonstrated that the LLPS of SGs can be regulated by intracellular dynamics in two stages: the reduced intracellular diffusion promotes SG assembly and the microtubule-associated transport facilitates SG coalescences. The work on intracellular dynamics not only improves the understanding of the mechanism of physiology phase separations occurring in nonequilibrium environments but also reveals an interplay between intracellular dynamics and LLPS., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Quantum dots are nanoparticles (2-10 nm) that emit strong and tunable fluorescence. Quantum dots have been heavily used in high-demand commercialized products, research, and for medical purposes. Emerging concerns have demonstrated the negative impact of quantum dots on living cells; however, the intracellular trafficking of QDs in yeast cells and the effect of this interaction remains unclear. The primary goal of our research is to investigate the trafficking path of red cadmium selenide zinc sulfide quantum dots (CdSe/ZnS QDs) in Saccharomyces cerevisiae and the impact QDs have on yeast cellular dynamics. Using cells with GFP-tagged reference organelle markers and confocal microscopy, we were able to track the internalization of QDs. We found that QDs initially aggregate at the exterior of yeast cells, enter the cell using clathrin-receptor-mediated endocytosis, and distribute at the late Golgi/trans-Golgi network. We also found that the treatment of red CdSe/ZnS QDs resulted in growth rate reduction and loss of polarized growth in yeast cells. Our RNA sequence analysis revealed many altered genes. Particularly, we found an upregulation of DID2 , which has previously been associated with cell cycle arrest when overexpressed, and a downregulation of APS2 , a gene that codes for a subunit of AP2 protein important for the recruitment of proteins to clathrin-mediated endocytosis vesicle. Furthermore, CdSe/ZnS QDs treatment resulted in a slightly delayed endocytosis and altered the actin dynamics in yeast cells. We found that QDs caused an increased level of F-actin and a significant reduction in profilin protein expression. In addition, there was a significant elevation in the amount of coronin protein expressed, while the level of cofilin was unchanged. Altogether, this suggests that QDs favor the assembly of actin filaments. Overall, this study provides a novel toxicity mechanism of red CdSe/ZnS QDs on yeast actin dynamics and cellular processes, including endocytosis.

Nanocolloids that are cumulatively referred to as nanocarbons, attracted significant attention during the last decade because of facile synthesis methods, water solubility, tunable photoluminescence, easy surface modification, and high biocompatibility. Among the latest development in this reserach area are chiral nanocarbons exemplified by chiral carbon dots (CDots). They are expected to have applications in sensing, catalysis, imaging, and nanomedicine. However, the current methods of CDots synthesis show often contradictory chemical/optical properties and structural information that required a systematic study with careful structural evaluation. Here, we investigate and optimize chiroptical activity and photoluminescence of L- and D-CDots obtained by hydrothermal carbonization of L- and D-cysteine, respectively. Nuclear magnetic resonance spectroscopy demonstrates that they are formed via gradual dehydrogenation and condensation reactions of the starting amino acid leading to particles with a wide spectrum of functional groups including aromatic cycles. We found that the chiroptical activity of CDots has an inverse correlation with the synthesis duration and temperature, whereas the photoluminescence intensity has a direct one, which is associated with degree of carbonization. Also, our studies show that the hydrothermal synthesis of cysteine in the presence of boric acid leads to the formation of CDots rather than boron nitride nanoparticles as was previously proposed in several reports. These results can be used to design chiral carbon-based nanoparticles with optimal chemical, chiroptical, and photoluminescent properties., (© 2022 The Authors. Chirality published by Wiley Periodicals LLC.)

Quantum dots (QDs) are semiconducting nanoparticles having different optical and electrical properties when compared to larger particles. They exhibit photoluminescence when irradiated with ultraviolet light, which is due to the transition of an excited electron from the valence band to the conductance band followed by the return of the exciting electron back into the valence band. The size and material of QDs can affect their optical and other properties too. The QDs possess special attributes like high brightness, protection from photobleaching, photostability, color tunability, low toxicity, low production cost, a multiplexing limit, and a high surface-to-volume proportion, which make them a promising tool for biomedical applications. Here, in this study, we summarize the utilization of QDs in different applications including bioimaging, diagnostics, immunostaining, single-cell analysis, drug delivery, and protein detection. Moreover, we discuss the advantages and challenges of using QDs in biomedical applications when compared with other conventional tools., (© 2022 Deutsche Pharmazeutische Gesellschaft.)

Elucidating the biological behavior of engineered nanoparticles, for example, the protein corona, is important for the development of safe and efficient nanomedicine, but our current understanding is still limited due to its highly dynamic nature and lack of adequate analytical tools. In the present work, we demonstrate the establishment of a fluorescence resonance energy transfer (FRET)-based platform for monitoring the dynamic evolution behavior of the protein corona in complex biological media. With human serum albumin and lysozyme as the model serum proteins, the protein exchange process of the preformed corona on the surface of chiral quantum dots (QDs) upon feeding either individual protein or human serum was monitored in situ by FRET. Important parameters characterizing the evolution process of protein corona could be obtained upon quantitative analysis of FRET data. Further combining real-time FRET monitoring with gel electrophoresis experiments revealed that the nature of the protein initially adsorbed on the surface of QDs significantly affects the subsequent dynamic exchange behavior of the protein corona. Furthermore, our results also revealed that only a limited proportion of proteins are involved in the protein exchange, and the exchange process exhibits a significant dependence on the surface chirality of QDs. This work demonstrates the feasibility of FRET as a powerful tool to exploit the dynamic evolution process of the protein corona, which can provide theoretical guidance for further design of advanced nanomaterials for biomedical applications.

The use of indium phosphide (InP) quantum dots (QDs) as biological fluorophores is limited by the low photoluminescence quantum yield (ϕ PL ) and the lack of effective bioconjugation strategies. The former issue has been addressed by introducing a strain relaxing intermediate shell such as ZnSe, GaP etc. that significantly enhances the ϕ PL of InP. Herein, we present an effective strategy for the conjugation of emissive InP/GaP/ZnS QDs with a commonly used globular protein, namely bovine serum albumin (BSA), which generate colloidally stable QD bioconjugates, labeled as InP-BSA and demonstrate its use as energy transfer probes. The conjugate contains one protein per QD, and the circular dichroism spectra of BSA and InP-BSA exhibit similar fractions of α-helix and β-sheet, reflective of the fact that the secondary structure of the protein is intact on binding. More importantly, the fluorescence polarization studies corroborate the fact that the bound protein can hold a variety of chromophoric acceptors. Upon selectively exciting the InP-BSA component in the presence of bound chromophores, a reduction in the emission intensity of the donor is observed with a concomitant increase in emission of the acceptor. Time-resolved investigations further confirm an efficient nonradiative energy transfer from InP-BSA to the bound acceptors.

Background: Quantum dots (QDs) have gained increased attention for their extensive biomedical and electronic products applications. Due to the high priority of QDs in contacting the circulatory system, understanding the hemocompatibility of QDs is one of the most important aspects for their biosafety evaluation. Thus far, the effect of QDs on coagulation balance haven't been fully understood, and limited studies also have yet elucidated the potential mechanism from the perspective of interaction of QDs with coagulation-related proteins., Results: QDs induced the derangement of coagulation balance by prolonging the activated partial thromboplastin time and prothrombin time as well as changing the expression levels of coagulation and fibrinolytic factors. The contact of QDs with PTM (prothrombin), PLG (plasminogen) and FIB (fibrinogen) which are primary coagulation-related proteins in the coagulation and fibrinolysis systems formed QDs-protein conjugates through hydrogen-bonding and hydrophobic interaction. The affinity of proteins with QDs followed the order of PTM > PLG > FIB, and was larger with CdTe/ZnS QDs than CdTe QDs. Binding with QDs not only induced static fluorescence quenching of PTM, PLG and FIB, but also altered their conformational structures. The binding of QDs to the active sites of PTM, PLG and FIB may promote the activation of proteins, thus interfering the hemostasis and fibrinolysis processes., Conclusions: The interactions of QDs with PTM, PLG and FIB may be key contributors for interference of coagulation balance, that is helpful to achieve a reliable and comprehensive evaluation on the potential biological influence of QDs from the molecular level., (© 2022. The Author(s).)

Background: Quantum dots (QDs) have been used as fluorophores in various imaging fields owing to their strong fluorescent intensity, high quantum yield (QY), and narrow emission bandwidth. However, the application of QDs to bio-imaging is limited because the QY of QDs decreases substantially during the surface modification step for bio-application., Results: In this study, we fabricated alloy-typed core/shell CdSeZnS/ZnS quantum dots (alloy QDs) that showed higher quantum yield and stability during the surface modification for hydrophilization compared with conventional CdSe/CdS/ZnS multilayer quantum dots (MQDs). The structure of the alloy QDs was confirmed using time-of-flight medium-energy ion scattering spectroscopy. The alloy QDs exhibited strong fluorescence and a high QY of 98.0%. After hydrophilic surface modification, the alloy QDs exhibited a QY of 84.7%, which is 1.5 times higher than that of MQDs. The QY was 77.8% after the alloy QDs were conjugated with folic acid (FA). Alloy QDs and MQDs, after conjugation with FA, were successfully used for targeting human KB cells. The alloy QDs exhibited a stronger fluorescence signal than MQD; these signals were retained in the popliteal lymph node area for 24 h., Conclusion: The alloy QDs maintained a higher QY in hydrophilization for biological applications than MQDs. And also, alloy QDs showed the potential as nanoprobes for highly sensitive bioimaging analysis., (© 2022. The Author(s).)

The development of QDs-based fluorescent bionanoprobe for cellular imaging fundamentally relies upon the precise knowledge of particle-cell interaction, optical properties of QDs inside and outside of the cell, movement of a particle in and out of the cell, and the fate of particle. We reported engineering and physicochemical characterization of water-dispersible Eu 3+ /Mn 2+ co-doped ZnSe@ZnS core/shell QDs and studied their potential as a bionanoprobe for biomedical applications, evaluating their biocompatibility, fluorescence behaviour by CytoViva dual mode fluorescence imaging, time-dependent uptake, endocytosis and exocytosis in RAW 264.7 macrophages. The oxidation state and local atomic structure of the Eu dopant studied by X-ray absorption fine structure (XAFS) analysis manifested that the Eu 3+ ions occupied sites in both ZnSe and ZnS lattices for the core/shell QDs. A novel approach was developed to relieve the excitation constraint of wide bandgap ZnSe by co-incorporation of Eu 3+ /Mn 2+ codopants, enabling the QDs to be excited at a wide UV-visible range. The QDs displayed tunable emission colors by a gradual increase in Eu 3+ concentration at a fixed amount of Mn 2+ , systematically enhancing the Mn 2+ emission intensity via energy transfer from the Eu 3+ to Mn 2+ ion. The ZnSe:Eu 3+ /Mn 2+ @ZnS QDs presented high cell viability above 85% and induced no cell activation. The detailed analyses of QDs-treated cells by dual mode fluorescence CytoViva microscopy confirmed the systematic color-tunable fluorescence and its intensity enhances as a function of incubation time. The QDs were internalized by the cells predominantly via macropinocytosis and other lipid raft-mediated endocytic pathways, retaining an efficient amount for 24 h. The unique color tunability and consistent high intensity emission make these QDs useful for developing a multiplex fluorescent bionanoprobe, activatable in wide-visible region.

Doping quantum dots (QDs) with extra element presents a promising future for their applications in the fields of environmental monitoring, commercial products and biomedical sciences. However, it remains unknown for the influence of doping on the molecular biocompatibility of QDs and the underlying mechanisms of the interaction between doped-QDs and protein molecules. Using the "one-pot" method, we synthesized N-acetyl-l-cysteine capped CdTe: Zn 2+ QDs with higher fluorescence quantum yield, improved stability and better molecular biocompatibility compared with undoped CdTe QDs. Using digestive enzyme trypsin (TRY) as the protein model, the interactions of undoped QDs and Zn-doped QDs with TRY as well as the underlying mechanisms were investigated using multi-spectroscopy, isothermal titration calorimetry and dialysis techniques. Van der Waals forces and hydrogen bonds are the major driving forces in the interaction of both QDs with TRY, which leading to the loosening of protein skeleton and tertiary structural changes. Compared with undoped QDs, Zn-doped QDs bind less amount of TRY with a higher affinity and then release higher amount of Cd. Zn-doped QDs have a less stimulating impact on TRY activity by decreasing TRY binding and reducing Cd binding to TRY. Taken all together, Zn-doped QDs offer a safer alternative for the applications of QDs by reducing unwanted interactions with proteins and improving biocompatibility at the molecular level., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Quantum dots (QDs) are crystalline inorganic semiconductor nanoparticles a few nanometers in size that possess unique optical electronic properties vs those of larger materials. For example, QDs usually exhibit a strong and long-lived photoluminescence emission, a feature dependent on size, shape and composition. These special optoelectronic properties make them a promising alternative to conventional luminescent dyes as optical labels in biomedical applications including biomarker quantification, biomolecule targeting and molecular imaging. A key parameter for use of QDs is to functionalize their surface with suitable (bio)molecules to provide stability in aqueous solutions and efficient and selective tagging biomolecules of interest. Researchers have successfully developed biocompatible QDs and have linked them to various biomolecule recognition elements, i.e., antibodies, proteins, DNA, etc. In this chapter, QD synthesis and characterization strategies are reviewed as well as the development of nanoplatforms for luminescent biosensing and imaging-guided targeting. Relevant biomedical applications are highlighted with a particular focus on recent progress in ultrasensitive detection of clinical biomarkers. Finally, key future research goals to functionalize QDs as diagnostic tools are explored., (Copyright © 2022 Elsevier Inc. All rights reserved.)

As a newly developed cadmium-free quantum dot (QD), CuInS 2 /ZnS has great application potential in many fields, but its biological safety has not been fully understood. In this study, the in vitro toxicity of CuInS 2 /ZnS QDs on U87 human glioma cell line was explored. The cells were treated with different concentrations of QDs (12.5, 25, 50 and 100 μg/mL), and the uptake of QDs by the U87 cells was detected by fluorescence imaging and flow cytometry. The cell viability was observed by MTT assay, and the gene expression profile was analyzed by transcriptome sequencing. These results showed that QDs could enter the cells and mainly located in the cytoplasm. The uptake rate was over 90 % when the concentration of QDs reached 25 μg/mL. The cell viability (50 and 100 μg/mL) increased at 24 h (P < 0.05), but no significant difference after 48 h and 72 h treatment. The results of differential transcription showed that coding RNA accounted for the largest proportion (62.15 %), followed by long non-coding RNA (18.65 %). Total 220 genes were up-regulated and 1515 genes were down-regulated, and significantly altered gene functions included nucleosome, chromosome-DNA binding, and chromosome assembly. In conclusion, CuInS 2 /ZnS QDs could enter U87 cells, did not reduce the cell viability, but would obviously alter the gene expression profile. These findings provide valuable information for a proper understanding of the toxicity risk of CuInS 2 /ZnS QD and promote the rational utilization of QDs in the future., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Carbon dots (CDs) are widely used in cell imaging due to their excellent optical properties, biocompatibility and low toxicity. At present, most of the research on CDs focuses on biomedical application, while there are few studies on the application of microbial imaging., Results: In this study, B- and N-doped carbon dots (BN-CDs) were prepared from citric acid, ethylenediamine, and boric acid by microwave hydrothermal method. Based on BN-CDs labeling yeast, the dead or living of yeast cell could be quickly identified, and their growth status could also be clearly observed. In order to further observe the morphology of yeast cell under different lethal methods, six methods were used to kill the cells and then used BN-CDs to label the cells for imaging. More remarkably, imaging of yeast cell with ultrasound and antibiotics was significantly different from other imaging due to the overflow of cell contents. In addition, the endocytosis mechanism of BN-CDs was investigated. The cellular uptake of BN-CDs is dose, time and partially energy-dependent along with the involvement of passive diffusion. The main mechanism of endocytosis is caveolae-mediated., Conclusion: BN-CDs can be used for long-term stable imaging of yeast, and the study provides basic research for applying CDs to microbiol imaging., (© 2021. The Author(s).)

Alzheimer's disease (AD) is a primary form of dementia with debilitating consequences, but no effective cure is available. While the pathophysiology of AD remains multifactorial, the aggregation of amyloid beta (Aβ) mediated by the cell membrane is known to be the cause for the neurodegeneration associated with AD. Here we examined the effects of graphene quantum dots (GQDs) on the obstruction of the membrane axis of Aβ in its three representative forms of monomers (Aβ-m), oligomers (Aβ-o), and amyloid fibrils (Aβ-f). Specifically, we determined the membrane fluidity of neuroblastoma SH-SY5Y cells perturbed by the Aβ species, especially by the most toxic Aβ-o, and demonstrated their recovery by GQDs using confocal fluorescence microscopy. Our computational data through discrete molecular dynamics simulations further revealed energetically favorable association of the Aβ species with the GQDs in overcoming peptide-peptide aggregation. Overall, this study positively implicated GQDs as an effective agent in breaking down the membrane axis of Aβ, thereby circumventing adverse downstream events and offering a potential therapeutic solution for AD.

In living organisms, redox reactions play a crucial role in the progression of disorders accompanied by the overproduction of reactive oxygen and reactive chlorine species, such as hydrogen peroxide and hypochlorous acid, respectively. We demonstrate that green fluorescence graphene quantum dots (GQDs) can be employed for revealing the presence of the hypochlorous acid in aqueous solutions and cellular systems. Hypochlorous acid modifies the oxygen-containing groups of the GQD, predominantly opens epoxide ring C-O-C, forms excessive C=O bonds and damages the carbonic core of GQDs. These changes, which depend on the concentration of the hypochlorous acid and exposure time, manifest themselves in the absorbance and fluorescence spectra of the GQD, and in the fluorescence lifetime. We also show that the GQD fluorescence is not affected by hydrogen peroxide. This finding makes GQDs a promising sensing agent for selective detecting reactive chlorine species produced by neutrophils. Neutrophils actively accumulate GQDs allowing to visualize cells and to examine the redox processes via GQDs fluorescence. At high concentrations GQDs induce neutrophil activation and myeloperoxidase release, leading to the disruption of GQD structure by the produced hypochlorous acid. This makes the GQDs a biodegradable material suitable for various biomedical applications., (© 2021 IOP Publishing Ltd.)

Objectives: To investigate the pharmacokinetics, biodistribution and peritoneal retention of Ag2S quantum dots (Qds) after intraperitoneal (IP) injection into mice and to compare the results with those reported for the intravenous (IV) injection of these particles., Methods: Ag2S Qds was prepared by a simple one-step co-precipitation method and was injected intraperitoneally into mice. Six animals were sacrificed at predetermined time points, and blood, peritoneal content and tissue samples were collected. Ag concentration that represents the concentration of Qds was analysed by atomic absorption spectrophotometry., Key Findings: Detectability of Qds in the peritoneal sample up to 2 h indicated that, compared with small drug molecules, the absorption of Ag2S Qds from the peritoneal cavity occurred at a slower rate. The AUC tissue/AUC blood ratio in the liver and intestine after IP injection (0.55 and 0.98, respectively) was considerably lower than those for the bolus injection (217 and 94, respectively), while this ratio in the spleen and lungs was markedly higher than the IV route., Conclusions: Overall, the obtained results suggest that IP injection of Ag2S Qds could be more effective for drug delivery to/imaging of the spleen and lungs, whereas the IV injection for the drug delivery to/imaging of the liver and intestine., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As a class of functional proteins, enzymes possess inherent insignificant features, for instance, mediocre stability and membrane impermeability and reduced enzymatic activity after modification, which partly limit their biomedical applications. Thus, it is indispensable to exploit robust nanoreactors with high enzymatic activity and good stability and cell permeability. Here, the chiral carbon dots (CDs)-glucose oxidase (GOx) nanoreactors named LGOx and DGOx were constructed by the coassembly of GOx with L/D-CDs, respectively. L/DGOx can significantly enhance the activity of GOx and improve the efficient delivery of GOx to cancer cells. Moreover, these nanoreactors can generate hydrogen peroxide to efficaciously kill cancer cells and restrain tumor growth, and DGOx exhibits higher enzymatic activity than LGOx. According to our understanding, this is the first report about utilizing chiral CDs as vectors to construct effective CDs-enzyme nanohybrids for cancer therapy, which is envisioned to be a versatile strategy for multitudinous biomedical applications.

Introduction: The biocompatibility and potential application of graphene-based nanomaterials in biomedicine have been documented. The effects of polyethylene glycol-graphene quantum dots (GQDs-PEG) on cardiac function in rats with myocardial infarction (MI) were examined., Methods: Wistar rats were randomly assigned to two main groups, each consisting of sham-Veh., MI-Veh., and MI+GQDs-PEG at doses of 5, 10, and 20 mg/kg. MI was induced by the closure of the left anterior descending (LAD) coronary artery. After MI, GQDs-PEG were injected at different doses IP every other day for two weeks. In the end, hemodynamic and heart contractility indices were assessed. The levels of myocardial MDA (malondialdehyde), SOD (superoxide dismutase), GPX (glutathione peroxidase), and TAC (total antioxidant capacity) were measured by the ELISA method. The serum ALP, ALT, AST, creatinine, and urea levels were measured using the photometric method. The infarct size was assessed by TTC staining., Results: GQDs-PEG decreased the infarct size at doses of 10 and 20 mg/kg and recovered the MI-induced reductions of +dp/dt max and -dp/dt max in the study groups. GQDs-PEG normalized systolic blood pressure and left ventricular systolic pressure reduction at the dose of 20 mg/kg in the MI group. Heart SOD, GPX, and TAC increased in the GQDs-PEG 10 and 20 groups. Almost no signs of toxic effects due to GQDs-PEG administration were observed on the liver and kidneys., Conclusions: The results provided clear evidence that GQDs-PEG improve cardiac performance and hemodynamic parameters in rats with MI by reducing oxidative stress. GQDs-PEG is proposed as a therapeutic target for the treatment of MI., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Farzaneh Rostamzadeh et al.)

A novel bifunctional carbon dot (CD)-based sensing platform was constructed for detection of tetracyclines (TCs) and Al 3+ . The fluorescence CDs were fabricated by hydrothermal method using phenylenediamine (p-PD) and ethylenebis(oxyethylenenitrilo) tetraacetic acid (EGTA) as precursors. The obtained prepared CDs show bright yellow fluorescence (y-CDs, E X  = 400 nm and Em = 556 nm), high fluorescence quantum yield (QY = 21.55 ± 0.06%), and preferable optical stability. TCs can directly quench the fluorescence of y-CDs based on static quenching characteristics and a small internal filtration effect (IEF). By adding Al 3+ to the y-CDs + TCs system, the fluorescence is partly recovered because TCs escape from the surface of the y-CDs and form a more stable chelate with Al 3+ . The sensing platform displays good selectivity and high sensitivity to TCs and Al 3+ with low detection limits of 0.057-0.23 μM and 0.091 μM, respectively. Importantly, this sensing platform has enabled the detection of TCs and Al 3+ in milk samples with satisfactory recoveries and RSDs, confirming the reliability and feasibility of this method. Combining with low toxicity and preferable biocompatibility, the y-CDs are extended to cellular imaging and detection of CTC and Al 3+ in A549 cells., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

This work focuses on the synthesis of novel modified core-shell CdTe/CdS quantum dots (QDs) and develops as a fluorescence sensor for glucose determination. The (E)-2,2'-(4,4'-dioxo-2,2'-dithioxo-2H,2'H-[5,5'-bithiazolylidene]-3,3'(4H,4'H)-diyl)bis(3- mercaptopropanoic acid) (DTM) as a new derivative of thiazolidine was synthesized and characterized and used to surface-modification of CdTe/CdS QDs. DTM-capped CdTe/CdS QDs used to immobilization of glucose oxidase (GOD). The intensity fluorescence emission of the CdSe/CdS-DTM/GOD is highly sensitive to the concentration of H 2 O 2 as a byproduct of the catalytic oxidation of glucose. The experimental results showed that the quenched fluorescence was proportional to the glucose concentration within the range of 10 nM-0.32 μM under optimized experimental conditions. The limit of detection of this system was found to be 4.3 nM. Compared with most of the existing methods, this newly developed system possesses many advantages, including simplicity, low cost, and good sensitivity., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ratiometric fluorescence (FL) probes are highly desirable for highly sensitive and reliable assays. Dual-emitting carbonized polymer dots (CPDs) have great application prospects in building ratiometric FL sensors. However, dual-emitting CPDs are usually synthesized at high temperatures and high pressures, which not only increases the cost but also complicates the structure of CPDs. Here, we developed a facile strategy for the fabrication of dual-emitting CPDs at room temperature using tetrachlorobenzoquinone and ethylenediamine. The formation of CPDs was induced by Schiff base condensation reaction, enabling the following cross-linking polymerization process. The dual-emitting CPDs demonstrate good photostability and antioxidant capacity. Importantly, the typical dual-emission bands of the as-prepared CPDs are found to have a blue emission band at 445 nm with a maximum excitation of 350 nm and a yellow emission band at 575 nm with a maximum excitation of 440 nm. Based on the dual-emitting property of CPDs, a ratiometric FL nanoprobe is obtained for sensitive determination of vitamin B12 (VB12), as the inner filtering and static quenching effects between VB12 and CPDs allow effective quenching of the blue FL of CPDs, while the yellow FL is maintained. The established assay shows linear detection ranges of 0.25-100 μM with a low limit of detection of 0.14 μM. These findings provide new guidance for the facile preparation of CPDs with excellent dual-emitting optical properties, indicating good prospects in biosensing.

In the present study, the novel Ag/cellulose nanocrystal (CNC)-doped CeO 2 quantum dots (QDs) with highly efficient catalytic performance were synthesized using one pot co-precipitation technique, which were then applied in the degradation of methylene blue and ciprofloxacin (MBCF) in wastewater. Catalytic activity against MBCF dye was significantly reduced (99.3%) for (4%) Ag dopant concentration in acidic medium. For Ag/CNC-doped CeO 2 vast inhibition domain of G-ve was significantly confirmed as (5.25-11.70 mm) and (7.15-13.60 mm), while medium- to high-concentration of CNC levels were calculated for G + ve (0.95 nm, 1.65 mm), respectively. Overall, (4%) Ag/CNC-doped CeO 2 revealed significant antimicrobial activity against G-ve relative to G + ve at both concentrations, respectively. Furthermore, in silico molecular docking studies were performed against selected enzyme targets dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and DNA gyrase belonging to folate and nucleic acid biosynthetic pathway, respectively to rationalize possible mechanism behind bactericidal potential of CNC-CeO 2 and Ag/CNC-CeO 2 ., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Nanotechnology has emerged as a promising solution to permanent elimination of cancer. However, nanoparticles themselves lack specificity to tumors. Due to enhanced migration to tumors, mesenchymal stem cells (MSCs) were suggested as cell-mediated delivery vehicles of nanoparticles. In this study, we have constructed a complex composed of photoluminescent quantum dots (QDs) and a photosensitizer chlorin e6 (Ce6) to obtain multifunctional nanoparticles, combining cancer diagnostic and therapeutic properties. QDs serve as energy donors-excited QDs transfer energy to the attached Ce6 via Förster resonance energy transfer, which in turn generates reactive oxygen species. Here, the physicochemical properties of the QD-Ce6 complex and singlet oxygen generation were measured, and the stability in protein-rich media was evaluated, showing that the complex remains the most stable in protein-free medium. In vitro studies on MSC and cancer cell response to the QD-Ce6 complex revealed the complex-loaded MSCs' potential to transport theranostic nanoparticles and induce cancer cell death. In vivo studies proved the therapeutic efficacy, as the survival of tumor-bearing mice was statistically significantly increased, while tumor progression and metastases were slowed down.

The oxidative properties of nanomaterials arouse legitimate concerns about oxidative damage in biological systems. On the other hand, the undisputable benefits of nanomaterials promote them for biomedical applications; thus, the strategies to reduce oxidative potential are urgently needed. We aimed at analysis of nitrogen-containing carbon quantum dots (N-CQDs) in terms of their biocompatibility and internalization by different cells. Surprisingly, N-CQD uptake does not contribute to the increased oxidative stress inside cells and lacks cytotoxic influence even at high concentrations, primarily through protein corona formation. We proved experimentally that the protein coating effectively limits the oxidative capacity of N-CQDs. Thus, N-CQDs served as an immobilization support for three different enzymes with the potential to be used as therapeutics. Various kinetic parameters of immobilized enzymes were analyzed. Regardless of the enzyme structure and type of reaction catalyzed, adsorption on the nanocarrier resulted in increased catalytic efficiency. The enzymatic-protein-to-nanomaterial ratio is the pivotal factor determining the course of kinetic parameter changes that can be tailored for enzyme application. We conclude that the above properties of N-CQDs make them an ideal support for enzymatic drugs required for multiple biomedical applications, including personalized medical therapies.

At present, the complex pathogenesis, the difficult-to-overcome blood-brain barrier (BBB), the development of the disease course which cannot be prevented, and other problems are serious challenges in the treatment of Alzheimer's disease (AD). In order to enhance the therapeutic effect of drugs through BBB, we synthesized simple and easy-to-obtain selenium quantum dots (SeQDs), with a multitarget therapeutic effect. This new type of SeQDs has an ultrasmall size and can quickly penetrate the BBB. According to the fluorescence characteristics of SeQDs, we can diagnose and track AD. The experimental results show that SeQDs have strong free-radical scavenging activity, protect cells from oxidative stress induced by different stimuli, and show broad-spectrum antioxidant activity. The SeQDs can not only effectively inhibit Aβ aggregation and significantly reduce Aβ-mediated cytotoxicity, thus preventing AD cascade reaction, but also effectively reduce tau protein phosphorylation by down-regulating PHF1 and CP13 and further reduce oxidative stress, restore mitochondrial functions, and maintain nerve cell stability and protect nerve cells from oxidative stress. In vivo studies demonstrate that SeQDs can continuously accumulate in the brain after rapid passage of BBB and can quickly alleviate AD, significantly improve the memory impairment of AD mice, and improve their learning and memory ability. Therefore, the use of SeQDs in the treatment of AD has great advantages compared with traditional single-target drugs and provides a new direction for the combination of prevention and treatment of neurodegenerative diseases.

During the last decades, there has been growing interest in using therapeutic messager RNA (mRNA) together with drug delivery systems. Naked, unformulated mRNA is, however, unable to cross the cell membrane and is susceptible to degradation. Here we use graphene quantum dots (GQDs) functionalized with polyethyleneimine (PEI) as a novel mRNA delivery system. Our results show that these modified GQDs can be used to deliver intact and functional mRNA to Huh-7 hepatocarcinoma cells at low doses and, that the GQDs are not toxic, although cellular toxicity is a problem for these first-generation modified particles. Functionalized GQDs represent a potentially interesting delivery system that is easy to manufacture, stable and effective., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

We demonstrate a versatile nanoparticle with imaging-guided chemo-photothermal synergistic therapy and EpCAM-targeted delivery of liver tumor cells. EpCAM antibody (anti-EpCAM) and Pt(IV) were grafted onto the polydopamine carbon dots (PDA-CDs) by the amidation reaction. The EpCAM antibody of particles enables the targeted interaction with liver progenitor cells due to their overexpressed EpCAM protein. The tetravalent platinum prodrug [Pt(IV)] induces apoptosis with minimum toxic side effects through the interaction between cisplatin and tumor cell DNA. The nanoparticles displayed stable photothermal property and considerable anti-tumor therapeutic effect in vivo . Coupling with cellular imaging due to their fluorescence property, anti-EpCAM@PDA-CDs@Pt(IV) offers a convenient and effective platform for imaging-guided chemo-photothermal synergistic therapy toward liver cancers in the near future.

Graphene quantum dots (GQDs) are emerging as a versatile nanomaterial with numerous proposed biomedical applications. Despite the explosion in potential applications, the molecular interactions between GQDs and complex biomolecular systems, including potassium-ion (K + ) channels, remain largely unknown. Here, we use molecular dynamics (MD) simulations and electrophysiology to study the interactions between GQDs and three representative K + channels, which participate in a variety of physiological processes and are closely related to many disease states. Using MD simulations, we observed that GQDs adopt distinct contact poses with each of the three structurally distinct K + channels. Our electrophysiological characterization of the effects of GQDs on channel currents revealed that GQDs interact with the extracellular voltage-sensing domain (VSD) of a Kv1.2 channel, augmenting current by left-shifting the voltage dependence of channel activation. In contrast, GQDs form a "lid" cluster over the extracellular mouth of inward rectifier Kir3.2, blocking the channel pore and decreasing the current in a concentration-dependent manner. Meanwhile, GQDs accumulate on the extracellular "cap domain" of K2P2 channels and have no apparent impact on the K + flux through the channel. These results reveal a surprising multifaceted regulation of K + channels by GQDs, which might help de novo design of nanomaterial-based channel probe openers/inhibitors that can be used to further discern channel function.

Blinking occurs with nearly all fluorophores including organic dyes, fluorescent proteins, semiconductor quantum dots and carbon dots (CDs). We developed non-blinking and photoresistant fluorescent CDs by introducing multiple aromatic domains onto a single carbon dot and demonstrated their great potential for imaging and tracking of receptors on a live cell membrane.

The olfactory system is a driver of feeding behavior, whereby olfactory acuity is modulated by the metabolic state of the individual. The excitability of the major output neurons of the olfactory bulb (OB) can be modulated through targeting a voltage-dependent potassium channel, Kv1.3, which responds to changes in metabolic factors such as insulin, glucose, and glucagon-like peptide-1. Because gene-targeted deletion or inhibition of Kv1.3 in the periphery has been found to increase energy metabolism and decrease body weight, we hypothesized that inhibition of Kv1.3 selectively in the OB could enhance excitability of the output neurons to evoke changes in energy homeostasis. We thereby employed metal-histidine coordination to self-assemble the Kv1.3 inhibitor margatoxin (MgTx) to fluorescent quantum dots (QDMgTx) as a means to label cells in vivo and test changes in neuronal excitability and metabolism when delivered to the OB. Using patch-clamp electrophysiology to measure Kv1.3 properties in heterologously expressed cells and native mitral cells in OB slices, we found that QDMgTx had a fast rate of inhibition, but with a reduced IC 50, and increased action potential firing frequency. QDMgTx was capable of labeling cloned Kv1.3 channels but was not visible when delivered to native Kv1.3 in the OB. Diet-induced obese mice were observed to reduce body weight and clear glucose more quickly following osmotic mini-pump delivery of QDMgTx/MgTx to the OB, and following MgTx delivery, they increased the use of fats as fuels (reduced respiratory exchange ratio). These results suggest that enhanced excitability of bulbar output neurons can drive metabolic responses., (© 2020 International Society for Neurochemistry.)

In this study, carbon dots (CDs) with red color are successfully prepared via hydrothermal treatment of o -phenylenediamine and urea. The as-prepared red CDs exhibit an acidichromism feature, making them turn purple at pH 4.4 and become blue at pH 3.3. Further investigations reveal that the surface chemical bond species of CDs are responsible for the acidichromism feature. Taking advantage of the acidichromism feature, the CDs are employed as a titration indicator for analysis of alkali samples, which gives rise to satisfactory results without significant difference between the titration methods using CDs and methyl orange or a mixture of methyl red and bromocresol green as indicators. The CDs show excitation-independent fluorescence with dual-emission at 600 and 650 nm, along with a respectable quantum yield of 20.1%, which provides the CDs with deep tissue penetration and minimum autofluorescence background that is desirable in bioimaging. In addition, the CDs are found to light up endoplasm reticulum particularly, indicating their endoplasm reticulum targeting capability, which is proven by a colocalization study with other classical subcellular dyes. Endocytosis inhibiting investigations confirm that the endoplasm reticulum targeting ability is mainly attributed to the caveolin/lipid-raft-mediated endocytosis pathways of CDs. This study not only presents a facile approach for red CDs but also explores the possibility of CDs in titration analysis and in endoplasm reticulum targeting imaging.

The outcome of radiotherapy is significantly restricted by tumor hypoxia. To overcome this obstacle, one prevalent solution is to increase intratumoral oxygen supply. However, its effectiveness is often limited by the high metabolic demand for O 2 by cancer cells. Herein, we develop a hybrid semiconducting organosilica-based O 2 nanoeconomizer pHPFON-NO/O 2 to combat tumor hypoxia. Our solution is twofold: first, the pHPFON-NO/O 2 interacts with the acidic tumor microenvironment to release NO for endogenous O 2 conservation; second, it releases O 2 in response to mild photothermal effect to enable exogenous O 2 infusion. Additionally, the photothermal effect can be increased to eradicate tumor residues with radioresistant properties due to other factors. This "reducing expenditure of O 2 and broadening sources" strategy significantly alleviates tumor hypoxia in multiple ways, greatly enhances the efficacy of radiotherapy both in vitro and in vivo, and demonstrates the synergy between on-demand temperature-controlled photothermal and oxygen-elevated radiotherapy for complete tumor response.

Photodynamic therapy (PDT), a non-invasive therapeutic modality, has received increasing attention owing to its high selectivity and limited side effects. Although significant clinical research progress has been made in PDT, the breadth and depth of its clinical application have not been fully realized due to the limitations such as inadequate light penetration depth, non-targeting photosensitizers (PSs), and tumor hypoxia. Consequently, numerous investigations put their emphasis on innovative strategies to overcome the aforementioned limitations and enhance the therapeutic effect of PDT. Herein, up-to-date advances in these innovative methods for PDT are summarized by introducing the design of PS systems, their working mechanisms and application examples. In addition, current challenges of these innovative strategies for clinical application, and future perspectives on further improvement of PDT are also discussed., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Selective discrimination and lasting tracking of live bacteria are primary steps for microbiology research and treatment of bacterial infection. However, conventional detection methods, such as the gold standard of Gram staining, are being challenged under actual test conditions. Herein, we provided a novel method, namely, three excitation peaks and single-color emission carbon quantum dots (T-SCQDs) for the rapid (5 min) peptidoglycan-targeting discrimination of Gram-positive bacteria and lasting tracking (24 h) through one-step staining. Bacterial viability testing indicates that T-SCQDs can achieve nondestructive identification of Gram-positive bacteria within 50-500 μg mL -1 . Interestingly, the fluorescence imaging system suggests that T-SCQDs can also selectively distinguish the type of colonies based on fluorescence intensity. Furthermore, T-SCQDs were successfully used to visually distinguish Gram-positive bacteria from the microbial environment of A549 cells by confocal fluorescence microscopy. These properties endow T-SCQDs with excellent functions for the diagnosis of infection and other biological applications.

This work demonstrates the application of hyaluronan-conjugated nitrogen-doped carbon quantum dots (HA-nCQDs) for bioimaging of tumor cells and illustrates their potential use as carriers in targeted drug delivery. Quantum dots are challenging to deliver with specificity, which hinders their application. To facilitate targeted internalization by cancer cells, hyaluronic acid, a natural ligand of CD44 receptors, was covalently grafted on nCQDs. The HA-nCQD conjugate was synthesized by carbodiimide coupling of the amine moieties on nCQDs and the carboxylic acids on HA chains. Conjugated HA-nCQD retained sufficient fluorescence, although with 30% lower quantum efficiency than the original nCQDs. Confocal microscopy showed enhanced internalization of HA-nCQDs, facilitated by CD44 receptors. To demonstrate the specificity of HA-nCQDs toward human tumor cells, patient-derived breast cancer tissue with high-CD44 expression was implanted in adult mice. The tumors were allowed to grow up to 200-250 mm 3 prior to the injection of HA-nCQDs. With either local or systemic injection, we achieved a high level of tumor specificity judged by a strong signal-to-noise ratio between the tumor and the surrounding tissue in vivo . Overall, the results show that HA-nCQDs can be used for imaging of CD44-specific tumors in preclinical models of human cancer and potentially used as carriers for targeted drug delivery into CD44-rich cells.

A wide variety of colloidal delivery systems, including polymeric nanoparticles, metal colloids, liposomes, and microemulsions have been reported to enhance the delivery of therapeutic agents across the nasal mucosa. The mechanisms involved in the uptake of these nanomaterials, especially ultrafine nanomaterials (diameters < 20 nm) through the nasal mucosa are not well understood. Fluorescent quantum dots (QDs) were used to investigate the uptake of ultrafine nanoparticles by bovine respiratory and olfactory mucosal tissues following in vitro exposure, and an inductively coupled plasma optical emission spectroscopy method was developed to quantify the amount of QDs localized within the tissues. QDs do not biodegrade or release their core materials and, as a result, this method allowed for the direct quantification of the nanoparticles themselves, rather than the measurement of a potentially dissociated drug or label. The results demonstrated that carboxylate-modified QDs (COOH-QDs) showed ∼2.5-fold greater accumulation in the epithelial and submucosal regions of olfactory tissues compared to that in respiratory tissues. Endocytic inhibitory studies showed that clathrin-dependent endocytosis, macropinocytosis, and caveolae-dependent endocytic process are all involved in the uptake of COOH-QDs into the respiratory tissues. In olfactory tissues, clathrin-dependent endocytosis is the major endocytic pathway involved in the uptake of COOH-QDs. Additional energy-independent pathways also appeared to allow the transfer of COOH-QDs within the olfactory mucosa. When polyethylene glycol-modified QDs known as PEGylated QDs (PEG-QDs) of similar size, ∼15 nm, were investigated, no nanoparticles were detected in the tissues suggesting that the PEG corona limits the interactions with endocytic and other uptake processes in the nasal epithelium. The capacity for nanoparticle uptake observed in the nasal mucosa, along with the ability of significant numbers of nanoparticles to enter the olfactory tissues using nonenergy-dependent pathways show that the pathways for ultrafine nanoparticle uptake in the nasal tissues have both drug delivery and toxicologic consequences. This places an increased importance on the careful selection of nanoparticle components and drugs intended for intranasal administration.

In this chapter we describe the use of fluorescent quantum dots (QDs) as labels for microbial mRNA transcripts using fluorescence in situ hybridization (FISH). Unlike organic dyes, which are the standard labels in modern FISH methods, QDs provide fluorescence signals that are much brighter and resistant to photobleaching, with an expanded spectral range for multiplexing. We describe the preparation of QDs with compact sizes necessary for accurate labeling, their application for analyzing lacZ transcripts in Escherichia coli cells using FISH, and an assessment of signal stability. We further discuss differences between methods for mammalian cells and bacteria, for which individual nucleic acids cannot be discretely counted due to the small cell size and the optical diffraction limit.

Tumor microenvironment turn-on nanoprobes that could specifically detect the occurrence of diseases possess great potential in early diagnosis. Here, a GSH activated nanoprobe was designed for fluorescence and 19 F magnetic resonance (MR) dual-modal turn-on imaging of tumors. Specifically, fluorescence AgInS 2 quantum dots (QDs for fluorescence imaging) were co-encapsulated with perfluoro-15-crown-5-ether (P 19 FCE for 19 F MRI) by amphiphilic polymers and further coated with in situ formed manganese dioxide (MnO 2 ) nanoshells, which served as efficient fluorescence and 19 F MR quenchers due to energy transfer and paramagnetic relaxation effects, respectively. The over-expressed GSH in tumors would decompose the MnO 2 nanoshells, resulting in remarkable enhancement of both fluorescence and 19 F MRI signals of the nanoprobes, accordingly lighting up the tumor site.

A robust platform is developed to assemble sub-10 nm organic aggregation-induced emission (AIE) particles using four different AIE luminogens (AIEgens) with emissions from green to the second near-infrared window (NIR-II). They are called AIE quantum dots (QDs) to distinguish from typical AIE dots which are larger than 25 nm. Compared with AIE dots that are larger than 25 nm, AIE QDs allow more efficient cellular uptake and imaging without surface modification of any membrane-penetrating peptides or other targeting molecules. NIR-II AIEgens, which have nearly no background fluorescence from organisms, are used to demonstrate that AIE QDs can achieve high contrast at the tumor as small as 80 mm 3 and evade the liver more efficiently than AIE dots. AIE QDs hold a good promise for sensitive and precise diagnosis of the latent solid tumor in clinical medicine with much lower off-targeting to the liver than AIE dots., (© 2020 Wiley-VCH GmbH.)

The bioaccumulation potential and toxic effects of engineered nanomaterials (ENMs) to earthworms are poorly understood. Two studies were conducted following OECD TG 222 on Eisenia fetida to assess the effects of CdTe QDs with different coatings and soil ageing respectively. Earthworms were exposed to carboxylate (COOH), ammonium (NH 4 + ), or polyethylene glycol (PEG) coated CdTe QDs, or a micron scale (bulk) CdTe material, at nominal concentrations of 50, 500 and 2000 mg CdTe QD kg -1 dry weight (dw) for 28 days in Lufa 2.2 soil. In the fresh soil study, earthworms accumulated similar amounts of Cd and Te in the CdTe-bulk exposures, while the accumulation of Cd was higher than Te during the exposures to CdTe QDs. However, neither the total Cd, nor Te concentrations in the earthworms, were easily explained by the extractable metal fractions in the soil or particle dissolution. There were no effects on survival, but some retardation of growth was observed at the higher doses. Inhibition of Na + / K + -ATPase activity with disturbances to tissue electrolytes, as well as tissue Cu and Mn were observed, but without depletion of total glutathione in the fresh soil experiment. Additionally, juvenile production was the most sensitive endpoint, with estimated nominal EC 50 of values >2000, 108, 65, 96 mg CdTe kg -1 for bulk, PEG-, COOH- and NH 4 + -coated CdTe QDs, respectively. In the aged soil study, the accumulation of Cd and Te was higher than in the fresh soil study in all CdTe QD exposures. Survival of the adult worms was reduced in the top CdTe-COOH and -NH 4 + QD exposures by 55 ± 5 and 60 ± 25%, respectively; and with decreases in growth. The nominal EC 50 values for juvenile production in the aged soil were 165, 88, 78 and 63 mg CdTe kg -1 for bulk, PEG-, COOH- and NH 4 + -coated CdTe QDs, respectively. In conclusion, exposure to nanoscale CdTe QDs, regardless of coating, caused more severe toxic effects that the CdTe bulk material and the toxicity increased after soil ageing. There were some coating-mediated effects, likely due to differences in the metal content and behaviour of the materials., Competing Interests: Declaration of competing interest The authors alone are responsible for the content and writing of the paper. The authors report no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

A paper-based visual fluorescence immunoassay is presented for the detection of matrix metalloproteinase-7 (MMP7) that is related to renal cancer. The method is based on the distance-dependent fluorescence quenching of CdTe quantum dots (QDs) on a nitrocellulose membrane by Ag + following a sandwich-type immunoreaction on microtiter wells using silver nanoparticle (AgNP)-labeled secondary antibody- and primary antibody-coated microtiter wells. The silver nanoparticles captured in the well are dissolved with HNO 3 , while the quenching effect of QDs is based on silver ion-exchange reaction under 365-nm excitation light irradiation. Increasing concentration of released Ag + , thus higher concentration of the protein, leads to an increased distance of quenching on the nitrocellulose membrane. The paper-based immunoassay by combination of AgNP-assisted ion-exchange reaction with QD gives good distance-dependent responses and allows the detection of MMP7 at a concentration as low as 7.3 pg mL -1 . The coefficients of variation are less than 6.9% and 12.4% for intra-assay and inter-assay, respectively. High specificity and long-term stability are achieved during the assay. Importantly, the testing of human serum samples using our strategy shows well-matched results with commercial human MMP7 ELISA kits. Graphical abstract A distance-dependent visual immunoassay is developed for the determination of serum matrix metalloproteinase-7 on CdTe quantum dot-impregnated paper with silver ion-exchange reaction.