Silver Selenide quantum dots (Ag2Se QDs) have great potential for biomedical applications due to their excellent optical properties, which has raised concerns about their health hazards. Previous studies have shown that exposure to Ag2Se QDs can induce neurotoxicity, but the underlying mechanisms have not been fully elucidated. In this study, Ag2Se QDs activated Nod-like receptor protein 3 (NLRP3) inflammasomes in microglia. Interestingly, we found that Ag2Se QDs-induced NLRP3 inflammasome activation was ferroptosis-dependent. Mechanistically, the overproduction of mitochondrial reactive oxygen species (mtROS) led to the leakage of mitochondrial DNA (mtDNA) into the cytoplasm via the open mitochondrial permeability transition pore (mPTP), thereby activating stimulator of interferon genes (STING)-dependent ferritinophagy. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy resulted in the degradation of ferritin heavy chain 1 (FTH1) and the release of iron ions, ultimately triggering ferroptosis. In order to assist in the risk assessment of Ag2Se QDs and the development of risk management strategies. Based on the above experimental data, we constructed an Adverse Outcome Pathway (AOP) framework for Ag2Se QDs neurotoxicity and emphasized the significance of alleviating mitochondrial damage in preventing neurotoxicity. Overall, the present study reveals new mechanisms of Ag2Se QDs-induced neurotoxicity. Meanwhile, this study provides insightful references for toxicity assessment and address.

Metal and metal oxide nanoparticles, owing to their unique physicochemical properties, have been extensively applied in biomedicine, cell labeling and sorting, drug delivery, and clinical therapy. Their impact on human health and environmental safety is increasingly drawing attention. These nanoparticles can enter the nervous system through multiple pathways, triggering the release of reactive oxygen species and cytokines, leading to blood-brain barrier damage and central nervous system dysfunction. This paper includes a methods section detailing literature search strategies, screening criteria, and time windows. It explores pathways for metal and metal oxide nanoparticles to enter the nervous system and their neurotoxic effects in vivo and in vitro. The influence of developmental stage and gender differences on the neurotoxicity of metal and metal oxide nanoparticles is clearly articulated. It systematically reviews and critically compares key molecular and cellular mechanisms underlying neurotoxicity induced by different types of metal and metal oxide nanoparticles, revealing their intrinsic connections and cascading effects. It critically evaluates particle effects versus ionic effects and grades the strength of particle-specific toxicity evidence. Factors influencing the toxicity of metal and metal oxide nanoparticles, including particle size, exposure concentration, and solubility are discussed. The neurotoxic characteristics and potential unique mechanisms distinguishing these nanoparticles from other nanomaterials are clarified. Possible mechanisms of neurotoxicity and physicochemical factors influencing toxicity are summarized, exploring how physicochemical properties determine interactions with the nervous system and toxicity severity. This review concludes by identifying existing challenges and future research directions regarding the neurotoxic effects of metal and metal oxide nanoparticles, providing a reference framework for their safety assessment and neurotoxicity studies.

Silver selenide quantum dots (Ag2Se QDs) show great advantages in tumor imaging due to their excellent optical performance and good biocompatibility. However, the ultrasmall particle size of Ag2Se QDs allows them to cross the blood-brain barrier, thus potentially affecting the central nervous system. Therefore, risk assessment and response strategies for Ag2Se QDs are important. The adverse outcome pathway (AOP) framework makes it possible to develop risk management strategies based on toxicity mechanisms. In this study, using the AOP framework, we constructed causal mechanism relationship diagrams at different biological levels of Ag2Se QD neurotoxicity. In this framework, excess mitochondrial reactive oxygen species (mtROS) triggered Nod-like receptor protein 3 (NLRP3) inflammasome activation in microglia was molecular initiation event (MIE). Proinflammatory mediator secretion and microglia activation were key events (KEs) at the cellular level. Neuroinflammation and neuronal damage were KEs at the organ/tissue level. Altered hippocampal physiology was the adverse outcome (AO) at the individual level. Based on the established AOP framework, further studies confirmed that mtROS-activated nuclear-factor-E2-related factor 2 (Nrf2)/PTEN-induced kinase 1 (PINK1)- mitophagy contributed to weaken the MIE. Molecular docking-assisted molecular biology experiments demonstrated that quercetin (Qu) enhanced this process. This article emphasizes the importance of the AOP in the risk management of nanomaterials. Furthermore, this paper guides the use of natural small-molecule drugs as a strategy to mitigate nanomaterial-induced neurotoxicity.

Quantum dots (QDs) are nanomaterials renowned for their exceptional optical properties and considerable potential in tumor imaging, drug delivery, and biosensing. These QDs can be functionalized with various ligands, including cetuximab, a monoclonal antibody that specifically targets the epidermal growth factor receptor (EGFR), commonly overexpressed in glioblastoma. Our research team has developed a cetuximab-conjugated CdTe/ZnS QD probe (CdTe/ZnS-Cet) and demonstrated its enhanced glioma imaging capabilities. In order to evaluate the neurotoxicity of the CdTe/ZnS-Cet probe in vivo, we conducted a series of studies using C. elegans as a model to detect the neurotoxicity of the probe. Our observations indicated a concentration-dependent impact of CdTe/ZnS-Cet on nematode physiological changes, with alterations in neurotransmitter levels (dopamine and glutamate) and related gene expression. It shows that these changes are closely associated with ROS-induced oxidative stress and mitochondrial damage. This study not only highlights the pivotal role of mitochondrial damage and ROS production of the CdTe/ZnS-Cet probe in C. elegans, but also provides new insights into the theoretical basis for reducing the neurotoxic effects of the CdTe/ZnS-Cet probe.

Cadmium telluride (CdTe) quantum dots (QDs) show great potential for biomedical applications owing to their excellent optical properties. Nevertheless, concerns about their potential neurotoxicity remain unanswered. Here, we conduct a systematic assessment. We study the biodistribution, neurobehavioral effects, and cellular responses in mice after tail vein injection of mercaptopropionic acid-modified CdTe QDs. The QDs display a blood clearance half-life of around 8 h. They mainly accumulate in the liver and kidneys and cross the blood-brain barrier within one hour, with the highest accumulation within the brain regions. Significantly, even though there is transient systemic toxicity, exposure to QDs triggers persistent neuroinflammation and causes substantial impairments in hippocampus-dependent learning and memory. To clarify the underlying mechanisms, we carried out single-cell RNA sequencing on hippocampal tissue. This high-resolution analysis uncovers a coordinated multicellular response, with microglia, oligodendrocyte precursors, and endothelial cells serving as key contributors to inflammatory, oxidative, and cellular stress pathways. These findings clarify the multicellular mechanisms underlying QD-induced neurotoxicity and establish a framework for assessing the neuro-safety of nanomaterials in biomedical settings.

The growing use of nanomaterials in industry and medicine raises significant concerns about their safety, particularly regarding their interactions with biological systems. Traditional toxicological methods, with limited throughput and mechanistic understanding, are increasingly being complemented by omics technologies. Genomics, transcriptomics, proteomics, and metabolomics provide comprehensive insights into the molecular mechanisms of nanomaterial toxicity and enable the identification of potential biomarkers. In addition, single-cell and spatial omics approaches are emerging as powerful tools to assess toxicity at the cellular and tissue levels, revealing heterogeneous responses and spatial distribution of nanomaterials. Despite their advantages, omics technologies face challenges in nanotoxicology, including large, complex data sets, integration difficulties, and a lack of standardized protocols. To address these challenges, we propose the development of new bioinformatics tools, multi-omics integration platforms, and standardized analysis processes to enhance research efficiency and accuracy. These efforts can provide a practical roadmap for integrating the application of omics technologies, including single-cell and spatial approaches, in the study of nanomaterial toxicity studies.

The toxic effects at the subcellular level of RSC96 cells after CdTe QDs exposure was still unclear. Meanwhile, whether the two classical mechanisms, oxidative stress and calcium ion overload, were involved in CdTe QDs-induced subcellular structural and functional dysfunction of RSC96 cells, which ultimately triggered cell death, remained to be verified. This research focused on the study of CdTe QDs exposure-induced oxidative stress in RSC96 cells, as well as the changes in intracellular calcium ion levels and intra-mitochondrial calcium ion levels. The subcellular structural and functional impairments of RSC96 cells induced by CdTe QDs exposure and the correlation of these impairments were further explored. In addition, the role of antioxidants and calcium chelators in maintaining RSC96 cell homeostasis under CdTe QDs exposure was also investigated. The results showed that 0-80 μM CdTe QDs exposure for 24 h induced oxidative stress and elevated Ca2+ concentration in RSC96 cells, which further caused endoplasmic reticulum expansion and mitochondria structural damage such as rupture of mitochondrial cristae and disappearance of cristae. Exposure to CdTe QDs in RSC96 cells induced endoplasmic reticulum stress and mitochondrial impairment, characterized by enhanced production of mtROS and a notable reduction in mitochondrial membrane potential. Intracellular Ca2+ overload and elevated mtROS concentration in mitochondria were closely associated with mitochondrial dysfunction and cell death triggered by exposure to CdTe QDs. Preincorporation of Mito-TEMPO mitigated the apoptosis rate of RSC96 cells and up-regulated the cellular ATP synthesizing capacity. Preincorporation of the Ca2+ chelator BAPTA-AM partially restored the cellular mitochondrial membrane potential, while decreasing the apoptosis rate of RSC96 cells.

The nervous system is very sensitive to CdTe quantum dots (CdTe QDs), and an understanding of the effects of CdTe QDs on the nervous system is indispensable for their use in biomedical applications, especially in clinical medicine. This research explored the possible neurotoxic effects of CdTe QDs on the peripheral nervous system of zebrafish, including motor neuron damage, altered mobility and motor behavior of zebrafish larvae. The mechanism of peripheral neurotoxicity induced by CdTe QDs was also investigated by qRT-PCR in this study. The experimental results showed that 100 nM and above quantum dot exposure induced shortening of axon length of motor neurons and reduced the length and number of neurogenesis as well as motor nerve branching in 24-120-hpf zebrafish. The toxic effects of 100 nM and above CdTe QDs on motor neurons were further manifested as a decrease in the overall activity level of the 144-hpf zebrafish larvae including decreased locomotor velocity and shortened movement time. The average swimming velocity and total movement time of zebrafish in the 400-nM CdTe QDs-treated group were 24.7% and 17.1% of those of the control group, respectively. Molecular toxicology studies showed that genes related to neurogenesis (nrd) and axonal growth (mbp, gfap, and gap43) were significantly affected by CdTe QDs exposure. Their expressions all tended to decrease in zebrafish larvae at 72 hpf after exposure to 400-nM CdTe QDs. In conclusion, the present study demonstrates that exposure of zebrafish to CdTe QDs at early life stages leads to adverse neural outcomes through inhibition of neural development and motor neuron axon growth.

Previous study has shown that CdTe QDs exposure reduced ND7/23 cells activity and induced cell apoptosis in a time-dependent manner. The mitochondrial pathway was involved in CdTe QDs-induced ND7/23 cell apoptosis. The toxic effects at the subcellular level of ND7/23 cells after CdTe QDs exposure was still unclear. Whether the two classical mechanisms, endoplasmic reticulum stress and calcium ion imbalance, were involved in the subcellular structural and functional dysfunction of ND7/23 cells induced by CdTe QDs, and whether the Ca2 + -calpain2 pathway played a significant role in the CdTe QDs-induced ND7/23 cell apoptosis remained to be validated. Therefore, this research focused on the study of CdTe QDs exposure-induced endoplasmic reticulum stress, organelle damage, and calcium homeostasis imbalance in ND7/23 cells. The apoptosis signaling pathway mediated by calpain2 and endoplasmic reticulum stress were also investigated. The results showed that exposure to 10 μM CdTe QDs for 0-24 h resulted in an increase in intracellular and mitochondrial Ca2+ concentration, accompanied by swelling of the endoplasmic reticulum and mitochondria and loss of mitochondrial cristae. CdTe QDs exposure also led to an increase in the expression of endoplasmic reticulum stress-related Bip protein. CdTe QDs exposure also initiated the up-regulation of calpain2 and cleaved-caspase7 protein expression, as well as cleavage of caspase12 and PARP proteins in ND7/23 cells. Addition of the calcium chelator BAPTA-AM and the calpeptin 2 inhibitor calpeptin significantly inhibited CdTe QDs-induced apoptosis and reversed the expression of these proteins. This study confirmed that exposure to CdTe QDs triggered endoplasmic reticulum stress in ND7/23 cells, along with the activation of the calpain2-caspase12 signaling pathway, resulting in mitochondria-independent apoptosis.

Abstract Background Recently, carbon quantum dots (CQDs) have been widely used in various fields, especially in the diagnosis and therapy of neurological disorders, due to their excellent prospects. However, the associated inevitable exposure of CQDs to the environment and the public could have serious severe consequences limiting their safe application and sustainable development. Results In this study, we found that intranasal treatment of 5 mg/kg BW (20 µL/nose of 0.5 mg/mL) CQDs affected the distribution of multiple metabolites and associated pathways in the brain of mice through the airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) technique, which proved effective in discovery has proven to be significantly alerted and research into tissue-specific toxic biomarkers and molecular toxicity analysis. The neurotoxic biomarkers of CQDs identified by MSI analysis mainly contained aminos, lipids and lipid-like molecules which are involved in arginine and proline metabolism, biosynthesis of unsaturated fatty acids, and glutamine and glutamate metabolism, etc. as well as related metabolic enzymes. The levels or expressions of these metabolites and enzymes changed by CQDs in different brain regions would induce neuroinflammation, organelle damage, oxidative stress and multiple programmed cell deaths (PCDs), leading to neurodegeneration, such as Parkinson’s disease-like symptoms. This study enlightened risk assessments and interventions of QD-type or carbon-based nanoparticles on the nervous system based on toxic biomarkers regarding region-specific profiling of altered metabolic signatures. Conclusion These findings provide information to advance knowledge of neurotoxic effects of CQDs and guide their further safety evaluation.

The increasing application of quantum dots (QDs) increases interactions with organisms. The inflammatory imbalance is a significant manifestation of immunotoxicity. Macrophages maintain inflammatory homeostasis. Using macrophages differentiated by phorbol 12-myristate 13-acetate-induced THP-1 cells as models, the study found that low-dose (5 mu M) cadmium telluride QDs (CdTe-QDs) hindered monocyte -macrophage differentiation. CD11b is a surface marker of macrophage, and the addition of CdTe-QDs during induction resulted in a decrease in CD11b expression. Moreover, exposure of differentiated THP-1 macrophage (dTHP-1) to 5 mu M CdTe-QDs led to the initiation of M1 polarization. This was indicated by the increased surface marker CD86 expression, along with elevated level of NF- kappa B and IL-1 beta proteins. The potential mechanisms are being explored. The transcription factor EB (TFEB) plays a significant role in immune regulation and serves as a crucial regulator of the autophagic lysosomal pathway. After exposed to CdTe-QDs, TFEB activation-mediated autophagy and M1 polarization were observed to occur simultaneously in dTHP-1. The mTOR signaling pathway contributed to TFEB activation induced by CdTe-QDs. However, mTOR-independent activation of TFEB failed to promote M1 polarization. These results suggest that mTOR-TFEB is an advantageous target to enhance the biocompatibility of CdTe-QDs.

Silver nanoparticles (AgNPs) have been widely used in biomedicine and cosmetics, increasing their potential risks in neurotoxicity. But the involved molecular mechanism remains unclear. This study aims to explore molecular events related to AgNPs-induced neuronal damage by RNA-seq, and elucidate the role of Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells synaptic degeneration induced by AgNPs. This study found that cell viabilities were decreased by AgNPs in a dose/time-dependent manner. AgNPs also increased protein expression of PINK1, Parkin, synaptophysin, and inhibited PGC-1 alpha, MAP2 and APP protein expression, indicating AgNPs-induced synaptic degeneration involved in disturbance of mitophagy and mitochondrial biogenesis in HT22 cells. Moreover, inhibition of AgNPs-induced Ca2+/CaMKII activation and Drp1/ ROS rescued mitophagy disturbance and synaptic degeneration in HT22 cells by reserving aforementioned protein express changes except for PGC-1 alpha and APP protein. Thus, AgNPs-induced synaptic degeneration was mediated by Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells, and mitophagy is the sensitive to the mechanism. Our study will provide in-depth molecular mechanism data for neurotoxic evaluation and biomedical application of AgNPs.

Reproductive disorders and declining fertility rates are significant public health concerns affecting birth rates and future populations. Male infertility, often due to spermatogenesis defects, may be linked to environmental pollutants like nickel nanoparticles (Ni NPs). Ni NPs are extensively utilized across different industries. Nevertheless, their potential adverse effects cannot be overlooked. Previous studies have linked the reproductive toxicity induced by Ni NPs with disturbances in mitochondrial function. Mitochondrial division/fusion dynamics are crucial to their proper function, yet little is known about how Ni NPs perturb these dynamics and whether such perturbation contributes to the impairment of the male reproductive system. Herein, we demonstrated that the exposure of Ni NPs to the mouse-derived spermatogonia cell line (GC-1 cells) triggered DRP1-mediated mitochondrial division and the enhanced impairment of mitochondria, consequently promoting mitochondria-dependent cell apoptosis. Notably, both the mitochondrial division inhibitor (Mdivi-1) and lentiviral-transfected cells with low expression of Dnm1l-DK in these cells could mitigate the toxic effects induced by Ni NPs, pointing to the potential role of mitochondrial dynamics in Ni NP-induced reproductive toxicity. Collectively, our work contributes to the understanding of the mechanisms by which Ni NPs can impact male reproductive function and identifies mitochondrial division as a potential target for intervention.

The early-stage diagnosis and therapy of brain diseases pose a persistent challenge in the field of biomedicine. Quantum dots (QDs), nano-luminescent materials known for their small size and fluorescence imaging capabilities, present promising capabilities for diagnosing, monitoring, and treating brain diseases. Although some investigations about QDs have been conducted in clinical trials, the concerns about the toxicity of QDs have continued. In addition, the lack of effective toxicity evaluation methods and systems and the difference between in vivo and in vitro toxicity evaluation hinder QDs application. The primary objective of this paper is to introduce the neurotoxic effects and mechanisms attributable to QDs. First, we elucidate the utilization of QDs in brain disorders. Second, we sketch out three pathways through which QDs traverse into brain tissue. Ultimately, expound upon the adverse consequences of QDs on the brain and the mechanism of neurotoxicity in depth. Finally, we provide a comprehensive summary and outlook on the potential development of quantum dots in neurotoxicity and the difficulties to be overcome.

Generated from plastics, microplastics (MPs) and nanoplastics (NPs) are difficult to completely degrade in the natural environment, which can accumulate in almost all lives. Liver is one of the main target organs. In this study, HepG2 and L02 cells were exposed to 0-50 mu g/mL polystyrene (PS)-NPs to investigate the mechanism of mitochondrial damage and inflammation. The results showed mitochondria damage and inflammatory caused by NPs, and it can be inhibited by N-acetyl-L-cysteine (NAC). In addition, reactive oxygen species (ROS) activated nuclear factor erythroid-derived factor 2-related factor (Nrf2) pathway. Nrf2 siRNA exacerbated the injury, suggesting Nrf2 plays a protective role. Moreover, p62 siRNA increased ROS and mitochondrial damage by inhibiting Nrf2, but didn't affect the inflammation. In conclusion, Nrf2 was activated by ROS and played a protective role in PS-NPs-mediated hepatotoxicity. This study supplemented the data of liver injury caused by PSNPs, providing a basis for the safe disposal of plastics.

With the widespread use of antimony compounds in synthetic materials and processing, the occupational exposure and environmental pollution caused by antimony have attracted the attention of researchers. Studies have shown that antimony compounds can cause liver damage, but the mechanism has not yet been elucidated. In this study, we used the trivalent potassium antimony tartrate (PAT) to infect L02 hepatocytes and Kunming (KM) mice to establish an antimony-induced apoptosis model of L02 cells and a subacute liver injury model of KM mice. We found that PAT exposure caused hepatocyte apoptosis and was accompanied by oxidative stress and endoplasmic reticulum stress (ERS), and the ERS-associated PERK pathway was activated. Further experimental results showed that N-acetyl-l-cysteine (NAC) pretreatment or silencing of the PERK gene in L02 cells reduced PAT-induced apoptosis. The activity of SOD and CAT in treated L02 cells was increased, the malondialdehyde content in L02 cells and liver tissues was decreased, and the content of ERS-related proteins GRP78 and CHOP, as well as the content of PERK-pathway-related proteins p-PERK/PERK, p-eif2α/eif2α and ATF4 protein were significantly reduced. Overall, PAT exposure triggered hepatocyte apoptosis and liver injury by inducing oxidative stress and activating the ERS-associated PERK pathway; however, this effect could be alleviated by NAC intervention or silencing of PERK in hepatocytes.

Cadmium telluride (CdTe) quantum dots (QDs) have garnered significant attention for tumor imaging due to their exceptional properties. However, there remains a need for further investigation into their potential toxicity mechanisms and corresponding enhancements. Herein, CdTe QDs were observed to accumulate in mouse liver, leading to a remarkable overproduction of IL-1 beta and IL-6. Additionally, there was evidence of macrophage infiltration and activation following exposure to 12.5 mu mol/kg body weight of QDs. To elucidate the underlying mechanism of macrophage activation, CdTe QDs functionalized with 3-mercaptopropionic acid (MPA) were utilized. In vitro experiments revealed that 1.0 mu M MPA-CdTe QDs activated PINK1-dependent mitophagy in RAW264.7 macrophages. Critically, the autophagic flux remained unimpeded, as demonstrated by the absence of p62 accumulation, LC3 turnover assay results, and successful fusion of autophagosomes with lysosomes. Mechanically, QDs increased reactive oxygen species (ROS) and mitoROS by damaging both mitochondria and lysosomes. ROS, in turn, inhibited NRF2, resulting in the phosphorylation of ERK1/2 and subsequent activation of mitophagy. Notably, 1.0 mu M QDs disrupted lysosomes but autophagic flux was not impaired. Eventually, the involvement of the ROS-NRF2-ERK1/2 pathway-mediated mitophagy in the increase of IL-1 beta and IL-6 in macrophages was confirmed using Trolox, MitoTEMPO, ML385, specific siRNAs, and lentivirus-based interventions. This study innovatively revealed the pro-inflammatory rather than anti-inflammatory role of mitophagy in nanotoxicology, shedding new light on the mechanisms of mitochondrial disorders induced by QDs and identifying several molecular targets to comprehend the toxicological mechanisms of CdTe QDs.

Ambient particulate matter (PM) exposure is a known risk factor for cardiovascular diseases. Epidemiological studies have shown the association between PM exposure and vascular complications, including vasculitis, embolism, hypertension, stroke, and atherosclerosis. However, the exact mechanisms underlying its vascular toxicity, especially in relation to short-term exposures, remain incompletely understood. This study investigates the role of PM and its carbonaceous cores in driving vascular endothelial inflammation via inflammasome activation. We hypothesized that PM SRM1648a exposure induces vascular endothelial inflammation through oxidative stress and inflammasome activation. Short-term exposure to PM SRM1648a was assessed in BALB/c mice for systemic inflammation and oxidative stress biomarkers, alongside in vitro studies in HUVECs and EA.hy926 endothelial cells to elucidate inflammasome activation pathways. PM SRM1648a exposure significantly altered redox balance and cytokine profiles in mice and upregulated NLRP3/NLRC4 inflammasomes in vascular endothelial cells, leading to caspase-1/IL-1β activation. Intriguingly, pyroptosis was not the primary mode of cell death. In vitro studies demonstrated that antioxidants glutathione monoethyl ester effectively mitigated oxidative stress and inflammasome activation in endothelial cells. This study highlights the critical role of ROS-mediated inflammasome activation in vascular inflammation induced by PM SRM1648a, with carbon-based cores as key contributors.

Quantum dots (QDs) have significant potential for treating and diagnosing CNS diseases. Meanwhile, the neurotoxicity of QDs has garnered attention. In this review, we focus on elucidating the mechanisms and consequences of CNS oxidative stress induced by QDs. First, we discussed the pathway of QDs transit into the brain. We then elucidate the relationship between QDs and oxidative stress from in vivo and in vitro studies. Furthermore, the main reasons and adverse outcomes of QDs leading to oxidative stress are discussed. In addition, the primary factors that may affect the neurotoxicity of QDs are analyzed. Finally, we propose potential strategies for mitigating QDs neurotoxicity and outline future perspectives for their development.

Nano-bio interface is significant concern in nanomedicine. When nanoparticles (NPs) come into contact with cells, they form complexes with proteins known as protein corona (PC). Cadmium telluride quantum dots (CdTe QDs) have been applied as bioimaging probes and for macrophage theragnostic. However, the impact of protein corona on the behavior of CdTe QDs is not well understood. Macrophages play a crucial role in defending against NPs. In this study, RAW264.7 cells were used to investigated the inflammatory response in macrophages when exposed to CdTe QDs before and after PC formation in fetal bovine serum. The results indicated that protein corona polarized more macrophages towards M1 phenotype. Transcriptomics analysis revealed that PC-CdTe QDs altered a greater number of differentially expressed genes (DEGs) compared to CdTe QDs (177 and 398) at 1.0 μM in macrophages. The DEGs affected by PC-CdTe QDs contained several personalized inflammatory cytokines. The enriched pathways after PC formation included Cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, and TNF signaling pathway, etc. Furthermore, PC specifically exacerbated the overexpression of CCL2 and IL-1β proteins. Importantly, PC altered the mechanism of CdTe QD-induced pyroptosis, shifting it from activating NLRC4 to both NLRP1 and NLRP3 inflammasomes, and from cleaving GSDMD and GSDMB to GSDMB alone. Overall, protein corona exacerbated the inflammatory response induced by CdTe QDs in macrophages. This study provides valuable insight into the pro-inflammatory effect of protein corona on CdTe QDs, with implications for their use in bioimaging or macrophage theragnostic by either exploiting or eliminating this biological interface effect.