{"title":"HMGB1 derived from lung epithelial cells after cobalt nanoparticle exposure promotes the activation of lung fibroblasts.","authors":"Jiali Yuan,Yiqun Mo,Yue Zhang,Yuanbao Zhang,Qunwei Zhang","doi":"10.1080/17435390.2024.2404074","DOIUrl":"https://doi.org/10.1080/17435390.2024.2404074","url":null,"abstract":"We have previously demonstrated that exposure to cobalt nanoparticles (Nano-Co) caused extensive interstitial fibrosis and inflammatory cell infiltration in mouse lungs. However, the underlying mechanisms of Nano-Co-induced pulmonary fibrosis remain unclear. In this study, we investigated the role of high-mobility group box 1 (HMGB1) in the epithelial cell-fibroblast crosstalk in Nano-Co-induced pulmonary fibrosis. Our results showed that Nano-Co exposure caused remarkable production and release of HMGB1, as well as nuclear accumulation of HIF-1α in human bronchial epithelial cells (BEAS-2B) in a dose- and a time-dependent manner. Pretreatment with CAY10585, an inhibitor against HIF-1α, significantly blocked the overexpression of HMGB1 in cell lysate and the release of HMGB1 in the supernatant of BEAS-2B cells induced by Nano-Co exposure, indicating that Nano-Co exposure induces HIF-1α-dependent HMGB1 overexpression and release. In addition, treatment of lung fibroblasts (MRC-5) with conditioned media from Nano-Co-exposed BEAS-2B cells caused increased RAGE expression, MAPK signaling activation, and enhanced expression of fibrosis-associated proteins, such as fibronectin, collagen 1, and α-SMA. However, conditioned media from Nano-Co-exposed BEAS-2B cells with HMGB1 knockdown had no effects on the activation of MRC-5 fibroblasts. Finally, inhibition of ERK1/2, p38, and JNK all abolished MRC-5 activation induced by conditioned media from Nano-Co-exposed BEAS-2B cells, suggesting that MAPK signaling might be a key downstream signal of HMGB1/RAGE to promote MRC-5 fibroblast activation. These findings have important implications for understanding the pro-fibrotic potential of Nano-Co.","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"26 1","pages":"1-17"},"PeriodicalIF":5.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inflammation related to inhalation of nano and micron sized iron oxides: a systematic review.","authors":"Aurora Moen,Helge Johnsen,Danail Hristozov,Alex Zabeo,Lisa Pizzol,Oihane Ibarrola,Gary Hannon,Sarah Holmes,Fikirte Debebe Zegeye,Ulla Vogel,Adriele Prina Mello,Shan Zienolddiny-Narui,Håkan Wallin","doi":"10.1080/17435390.2024.2399039","DOIUrl":"https://doi.org/10.1080/17435390.2024.2399039","url":null,"abstract":"Inhalation exposure to iron oxide occurs in many workplaces and respirable aerosols occur during thermal processes (e.g. welding, casting) or during abrasion of iron and steel products (e.g. cutting, grinding, machining, polishing, sanding) or during handling of iron oxide pigments. There is limited evidence of adverse effects in humans specifically linked to inhalation of iron oxides. This contrasts to oxides of other metals used to alloy or for coating of steel and iron of which several have been classified as being hazardous by international and national agencies. Such metal oxides are often present in the air at workplaces. In general, iron oxides might therefore be regarded as low-toxicity, low-solubility (LTLS) particles, and are often considered to be nontoxic even if very high and prolonged inhalation exposures might result in diseases. In animal studies, such exposures lead to cancer, fibrosis and other diseases. Our hypothesis was that pulmonary-workplace exposure during manufacture and handling of SPION preparations might be harmful. We therefore conducted a systematic review of the relevant literature to understand how iron oxides deposited in the lung are related to acute and subchronic pulmonary inflammation. We included one human and several in vivo animal studies published up to February 2023. We found 25 relevant studies that were useful for deriving occupational exposure limits (OEL) for iron oxides based on an inflammatory reaction. Our review of the scientific literature indicates that lowering of health-based occupational exposure limits might be considered.","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":"33 1","pages":"1-16"},"PeriodicalIF":5.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142268982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2024-09-01Epub Date: 2024-09-16DOI: 10.1080/17435390.2024.2401448
Jason William Grunberger, Marina A Dobrovolskaia, Hamidreza Ghandehari
{"title":"Immunological properties of silica nanoparticles: a structure-activity relationship study.","authors":"Jason William Grunberger, Marina A Dobrovolskaia, Hamidreza Ghandehari","doi":"10.1080/17435390.2024.2401448","DOIUrl":"10.1080/17435390.2024.2401448","url":null,"abstract":"<p><p>Silica nanoparticles are increasingly considered for drug delivery applications. These applications require an understanding of their biocompatibility, including their interactions with the immune system. However, systematic studies for silica nanoparticle immunological safety profiles are lacking. To fill this gap, we conducted an <i>in vitro</i> study investigating various aspects of silica nanoparticles' interactions with blood and immune cells. Four types of silica nanoparticles with variations in size and porosity were studied. These included nonporous Stöber silica nanoparticles with average diameters of approximately 50 and 100 nm (SNP50 and SNP100), mesoporous silica nanoparticles of approximately 100 nm (Meso100), and hollow mesoporous silica nanoparticles of approximately 100 nm (HMSNP100) in diameter, respectively. The hematological compatibility was assessed using hemolysis, complement activation, platelet aggregation, and plasma coagulation assays. The effects of nanoparticles on immune cell function were studied using <i>in vitro</i> phagocytosis, chemotaxis, natural killer cell cytotoxicity, leukocyte proliferation, human lymphocyte activation, colony-forming unit granulocyte-macrophage, and leukocyte procoagulant activity assays. The <i>in vitro</i> findings suggest that at high concentrations, corresponding to the <i>in vivo</i> human dose of 40 mg/kg, silica nanoparticles demonstrated an array of immunotoxic effects that depended on their physicochemical properties. However, all types of silica nanoparticles studied were not immunotoxic at concentrations corresponding to lower doses (≤ 8 mg/kg) comparable to that of nanocarriers in other nanomedicines currently used in the clinic. These findings are promising for using silica nanoparticles for the systemic delivery of bioactive and imaging agents.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"542-564"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2024-09-01Epub Date: 2024-09-23DOI: 10.1080/17435390.2024.2401430
C R Kirman, B Kent, J Bigelow, R A Canady, Q Chen, W C Chou, D Li, Z Lin, V Kumar, A Paini, P Poulin, L M Sweeney, S M Hays
{"title":"Physiologically based pharmacokinetic modeling of metal nanoparticles for risk assessment of inhalation exposures: a state-of-the-science expert panel review.","authors":"C R Kirman, B Kent, J Bigelow, R A Canady, Q Chen, W C Chou, D Li, Z Lin, V Kumar, A Paini, P Poulin, L M Sweeney, S M Hays","doi":"10.1080/17435390.2024.2401430","DOIUrl":"10.1080/17435390.2024.2401430","url":null,"abstract":"<p><p>A critical review of the current state-of-the-science for the physiologically based pharmacokinetic (PBPK) modeling of metal nanoparticles and their application to human health risk assessment for inhalation exposures was conducted. A systematic literature search was used to identify four model groups (defined as a primary publication along with multiple supplementary publications) subject to review. Using a recent guideline document from the Organization for Economic Cooperation and Development (OECD) for PBPK model evaluation, these model groups were critically peer-reviewed by an independent panel of experts to identify those to be considered for modeling and simulation application. Based upon the expert panel input, model confidence scores for the four model groups ranged from 30 to 41 (out of a maximum score of 50). The three highest-scoring model groups were then applied to compare predictions to a different metal nanoparticle (i.e. not specifically used to parameterize the original models) using a recently published data set for tissue burdens in rats, as well as predicting human tissue burdens expected for corresponding occupational exposures. Overall, the rat models performed reasonably well in predicting the lung but tended to overestimate systemic tissue burdens. Data needs for improving the state-of-the-science, including quantitative particle characterization in tissues, nanoparticle-corona data, long-term exposure data, interspecies extrapolation methods, and human biomonitoring/toxicokinetic data are discussed.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"527-541"},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2024-08-01Epub Date: 2024-08-05DOI: 10.1080/17435390.2024.2384408
Susann Wolf, Krishnan Sriram, Laura M A Camassa, Dhruba Pathak, Helene L Bing, Benedicte Mohr, Shan Zienolddiny-Narui, Johanna Samulin Erdem
{"title":"Systematic review of mechanistic evidence for TiO<sub>2</sub> nanoparticle-induced lung carcinogenicity.","authors":"Susann Wolf, Krishnan Sriram, Laura M A Camassa, Dhruba Pathak, Helene L Bing, Benedicte Mohr, Shan Zienolddiny-Narui, Johanna Samulin Erdem","doi":"10.1080/17435390.2024.2384408","DOIUrl":"10.1080/17435390.2024.2384408","url":null,"abstract":"<p><p>Nano-sized titanium dioxide particles (TiO<sub>2</sub> NPs) are a high-production volume nanomaterial widely used in the paints, cosmetics, food and photovoltaics industry. However, the potential carcinogenic effects of TiO<sub>2</sub> NPs in the lung are still unclear despite the vast number of <i>in vitro</i> and <i>in vivo</i> studies investigating TiO<sub>2</sub> NPs. Here, we systematically reviewed the existing <i>in vitro</i> and <i>in vivo</i> mechanistic evidence of TiO<sub>2</sub> NP lung carcinogenicity using the ten key characteristics of carcinogens for identifying and classifying carcinogens. A total of 346 studies qualified for the quality and reliability assessment, of which 206 were considered good quality. Using a weight-of-evidence approach, these studies provided mainly moderate to high confidence for the biological endpoints regarding genotoxicity, oxidative stress and chronic inflammation. A limited number of studies investigated other endpoints important to carcinogenesis, relating to proliferation and transformation, epigenetic alterations and receptor-mediated effects. In summary, TiO<sub>2</sub> NPs might possess the ability to induce chronic inflammation and oxidative stress, but it was challenging to compare the findings in the studies due to the wide variety of TiO<sub>2</sub> NPs differing in their physicochemical characteristics, formulation, exposure scenarios/test systems, and experimental protocols. Given the limited number of high-quality and high-reliability studies identified within this review, there is a lack of good enough mechanistic evidence for TiO<sub>2</sub> NP lung carcinogenicity. Future toxicology/carcinogenicity research must consider including positive controls, endotoxin testing (where necessary), statistical power analysis, and relevant biological endpoints, to improve the study quality and provide reliable data for evaluating TiO<sub>2</sub> NP-induced lung carcinogenicity.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"437-463"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2024-08-01Epub Date: 2024-08-02DOI: 10.1080/17435390.2024.2386019
Dharti Bhadla, Kinnari Parekh, Neeraj Jain
{"title":"Cytotoxic evaluation of pure and doped iron oxide nanoparticles on cancer cells: a magnetic fluid hyperthermia perspective.","authors":"Dharti Bhadla, Kinnari Parekh, Neeraj Jain","doi":"10.1080/17435390.2024.2386019","DOIUrl":"10.1080/17435390.2024.2386019","url":null,"abstract":"<p><p>The need of the hour with respect to cancer treatment is a targeted approach with minimal or nil ramifications. Apropos, magnetic fluid hyperthermia (MFH) is emerging as a potential therapeutic strategy with anticipated reduced side effects for solid tumors. MFH causes cytotoxicity due to the heat generated owing to Hysteresis, Neel, and Brownian relaxation losses once magnetic nanoparticles (MNPs) carrying cancer cells are placed under an alternating magnetic field. With respect to MFH, iron oxide-based MNPs have been most extensively studied to date compared to other metal oxides with magnetic properties. The effectiveness of MFH relies on the composition, coating, size, physical and biocompatible properties of the MNPs. Pure iron oxide and doped iron oxide MNPs have been utilized to study their effects on cancer cell killing through MFH. This review evaluates the biocompatibility of pure and doped iron oxide MNPs and their subsequent hyperthermic effect for effectively killing cancer cells in vitro and in vivo.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"464-478"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of polyethylene nanoplastics on human intestinal cells.","authors":"Wassim El Basset, Raphaël Cornu, Taghrid Zaiter, Léa Jacquin, Yann Pellequer, Brice Moulari, Mona Diab-Assaf, Fabrice Brunel, Vincent Monteil, Arnaud Béduneau","doi":"10.1080/17435390.2024.2393643","DOIUrl":"10.1080/17435390.2024.2393643","url":null,"abstract":"<p><p>Polyethylene (PE) is one of the most widely used plastics in the world. Its degradation leads to the production of small particles including microplastics and nanoplastics (NPs). Plastic particles' presence poses a health risk. The aim of this work was to investigate the toxicity of two model surfactant-free PE NPs prepared by polymerization of ethylene from cationic and anionic water-soluble initiators on human cell lines Caco-2 and HT29-MTX. After physicochemical characterization, their acute and subacute toxicity profile, including cytotoxicity, oxidative stress, and genotoxicity, was evaluated on both cell lines. Results showed a size increase of PE NPs in culture medium. Zeta potential values close to -10 mV were no longer dependent on the initiator charge after adsorption of serum components in culture medium. However, the cellular toxicity of the cationic and anionic PE NPs was very different. A time-and-concentration dependent cytotoxic, oxidative, and genotoxic effects on Caco-2 cells were only observed for PE NPs prepared with cationic initiators. No toxicity was observed on HT29-MTX, likely due to the protective mucus layer. Genotoxicity correlated with oxidative stress of some PE NPs on Caco-2 cells was observed from a concentration of 0.1 mg.mL<sup>-1</sup> after 48-h exposure.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"499-510"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Interaction between polydopamine-based IONPs and human serum albumin (HSA): a spectroscopic analysis with cytotoxicity impact.","authors":"Himanshu Shekhar, Priyatama Behera, Ashutosh Naik, Monalisa Mishra, Harekrushna Sahoo","doi":"10.1080/17435390.2024.2392579","DOIUrl":"10.1080/17435390.2024.2392579","url":null,"abstract":"<p><p>Iron oxide nanoparticles (IONPs) have been extensively explored in biomedicine, bio-sensing, hyperthermia, and drug/gene delivery, attributed to their versatile and tunable properties. However, owing to its numerous applications, the functionalization of IONPs with appropriate materials is in demand. To achieve optimal functionalization of IONPs, polydopamine (PDA) was utilized due to its ability to provide a superior functionalized surface, near-infrared light absorption, and adhesive nature to customize desired functionalized IONPs. This notion of involving PDA led to the successful synthesis of magnetite-PDA nanoparticles, where PDA is surface-coated on magnetite (Fe<sub>3</sub>O<sub>4</sub>@PDA). The Fe<sub>3</sub>O<sub>4</sub>@PDA nanoparticles were characterized using techniques like TEM, FESEM, PXRD, XPS, VSM, and FTIR, suggesting PDA's successful attachment with magnetite crystal structure retention. Human serum albumin (HSA), the predominant protein in blood plasma, interacts with the delivered nanoparticles. Therefore, we have employed various spectroscopic techniques, along with cytotoxicity, to inspect the effect of Fe<sub>3</sub>O<sub>4</sub>@PDA NPs on the stability and structure of HSA. The structural alterations were examined using circular dichroism (CD) and synchronous fluorescence spectroscopy (SFS). It has been observed that there are no structural perturbations in the secondary structure of the HSA protein after interaction with Fe<sub>3</sub>O<sub>4</sub>@PDA. Studies using steady-state fluorescence revealed that the inherent fluorescence intensities of HSA were suppressed after interaction with Fe<sub>3</sub>O<sub>4</sub>@PDA. In addition, temperature-dependent fluorescence measurements suggested that the type of quenching consists of both static and dynamic quenching simultaneously. A cytotoxicity study in <i>Drosophila melanogaster</i> larvae revealed no cytotoxic effects but did show a minor genotoxic effect only at higher concentrations.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"479-498"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2024-06-01Epub Date: 2024-06-07DOI: 10.1080/17435390.2024.2361687
Lily Yi Li, Elliya Park, Chunsheng He, Azhar Z Abbasi, Jeffrey T Henderson, Paul E Fraser, Jack P Uetrecht, Andrew M Rauth, Xiao Yu Wu
{"title":"Evaluation of the biodistribution and preliminary safety profile of a novel brain-targeted manganese dioxide-based nanotheranostic system for Alzheimer's disease.","authors":"Lily Yi Li, Elliya Park, Chunsheng He, Azhar Z Abbasi, Jeffrey T Henderson, Paul E Fraser, Jack P Uetrecht, Andrew M Rauth, Xiao Yu Wu","doi":"10.1080/17435390.2024.2361687","DOIUrl":"10.1080/17435390.2024.2361687","url":null,"abstract":"<p><p>A novel brain-targeted and reactive oxygen species-activatable manganese dioxide containing nanoparticle system functionalized with anti-amyloid-β antibody (named aAβ-BTRA-NC) developed by our group has shown great promise as a highly selective magnetic resonance imaging (MRI) contrast agent for early detection and multitargeted disease-modifying treatment of Alzheimer's disease (AD). To further evaluate the suitability of the formulation for future clinical application, we investigated the safety, biodistribution, and pharmacokinetic profile of aAβ-BTRA-NC in a transgenic TgCRND8 mouse AD model, wild type (WT) littermate, and CD-1 mice. Dose-ascending studies demonstrated that aAβ-BTRA-NC was well-tolerated by the animals up to 300 μmol Mn/kg body weight [b.w.], 3 times the efficacious dose for early AD detection without apparent adverse effects; Histopathological, hematological, and biochemical analyses indicated that a single dose of aAβ-BTRA-NC did not cause any toxicity in major organs. Immunotoxicity data showed that aAβ-BTRA-NC was safer than commercially available gadolinium-based MRI contrast agents at an equivalent dose of 100 μmol/kg b.w. of metal ions. Intravenously administered aAβ-BTRA-NC was taken up by main organs with the order of liver, kidneys, intestines, spleen, followed by other organs, and cleared after one day to one week post injection. Pharmacokinetic analysis indicated that the plasma concentration profile of aAβ-BTRA-NC followed a 2-compartmental model with faster clearance in the AD mice than in the WT mice. The results suggest that aAβ-BTRA-NC exhibits a strong safety profile as a nanotheranostic agent which warrants more robust preclinical development for future clinical applications.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"315-334"},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NanotoxicologyPub Date : 2024-06-01Epub Date: 2024-06-22DOI: 10.1080/17435390.2024.2369602
Xiao Tian, Yunpeng Zhang, Meng Zhang, Gang Liu, Yuedong Hao, Weidong Liu
{"title":"Nanoparticles-encapsulated doxorubicin alleviates drug resistance of osteosarcoma via inducing ferroptosis.","authors":"Xiao Tian, Yunpeng Zhang, Meng Zhang, Gang Liu, Yuedong Hao, Weidong Liu","doi":"10.1080/17435390.2024.2369602","DOIUrl":"10.1080/17435390.2024.2369602","url":null,"abstract":"<p><p>To determine the effects of polymeric nanoparticle for doxorubicin (Dox) delivery and treatment of drug-resistant Osteosarcoma (OS) cells. Methoxy-polyethylene glycol amino (mPEG-NH2) and platinum bio-mimetic polycaprolactone-cysteine (PtBMLC) were crosslinked to obtain glutathione (GSH)-responsive mPEG-NH2-PtBMLC polymer to encapsulate Dox (named as Nano-Dox). The particle size and zeta potential of the nanoparticles were measured, and internalization of Dox by OS cells was observed. After treatment with Nano-Dox, cell proliferation was determined by cell counting kit 8 (CCK-8) and colony formation assay. Cell migration and invasion were determined by Transwell assay. Cell cycle arrest was assessed by flow cytometry. The induction of ferroptosis was analyzed by abnormal accumulation of total iron, Fe2+. Nano-Dox exhibited a stronger localization in OS cells (<i>p</i> < 0.01). Nano-Dox induced more significant suppression of drug-resistant OS cell growth (<i>p</i> < 0.01), migration (<i>p</i> < 0.01), and invasion (<i>p</i> < 0.01), compared with the single Dox treatment group, along with decreased expression of N-cadherin, Snail, and Vimentin, suggesting impaired cancer migration and invasion. The treatment with Nano-Dox induced notable cell cycle arrest at G0/G1 phase (<i>p</i> < 0.01) and accumulation of iron, Fe2+, and MDA (<i>p</i> < 0.01), as well as suppressed the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11. Administration of ferroptosis inhibitor (Fer-1) reversed the anti-proliferation effects of Nano-Dox (<i>p</i> < 0.01). The Dox delivered by the polymeric nanoparticle system notably enhanced its effects on suppressing the growth, migration, and invasion of drug-resistant OS cells via inducing ferroptosis. The application of environment response polymer enhanced the delivery of Dox and the therapeutic effects on OS.</p>","PeriodicalId":18899,"journal":{"name":"Nanotoxicology","volume":" ","pages":"401-409"},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}