18 results on '"Qiyi Feng"'
Search Results
2. Impact of the expert consensus on polypharmacy and potentially inappropriate medication use in elderly lung cancer outpatients with multimorbidity: An interrupted time series analysis, 2016–2021
- Author
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Fangyuan Tian, Zhaoyan Chen, Rui Tang, Qiyi Feng, and Fengbo Wu
- Subjects
polypharmacy ,potentially inappropriate medication ,lung cancer ,elderly ,trend ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Objectives: Elderly lung cancer patients often have chronic diseases other than lung cancer. Therefore, this kind of population is often accompanied by polypharmacy. This situation and the resulting potentially inappropriate medication (PIM) use are an increasing global concern. In this context, the Chinese Association of Geriatric Research issued an expert consensus on the safety management of polypharmacy. However, the long- and short-term effects of the expert consensus on polypharmacy and PIM use are not clear.Methods: The study was conducted in Chengdu, a city in southwestern China, consisting of prescriptions for elderly lung cancer outpatients with multimorbidity (cancer with other diseases) from January 2016 to December 2021. The 2019 Beers criteria were used to evaluate PIM use, and interrupted time series analysis was used to evaluate the longitudinal effectiveness of expert consensus by measuring the prevalence of polypharmacy and PIM use. We used R software version 4.2.0 for data analysis.Results: A total of 7,238 elderly lung cancer outpatient prescriptions were included in the study. After the publication of the expert consensus, the level (β = -10.273, P < 0.001) of the prevalence of polypharmacy decreased, but the trend (β = 0.158, p = 0.855) of polypharmacy increased. The prevalence of PIM use decreased abruptly (β = -22.828, p < 0.001) after the intervention, but the long-term trend was still upward (β = 0.907, p = 0.916).Conclusion: The long-term effects of the publication of the expert consensus on the prevalence of polypharmacy and PIM use in hospitals in Chengdu were not optimal. Future research on interventions rationing polypharmacy and PIM use is needed.
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- 2022
- Full Text
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3. Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity
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Xuanming Chen, Cheng Shen, Zhe Wei, Rui Zhang, Yongsheng Wang, Lili Jiang, Ke Chen, Shuang Qiu, Yuanli Zhang, Ting Zhang, Bin Chen, Yanjun Xu, Qiyi Feng, Jinxing Huang, Zhihui Zhong, Hongxia Li, Guowei Che, and Kai Xiao
- Subjects
patient-derived xenograft (pdx) ,non-small cell lung cancer (nsclc) ,tumor heterogeneity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective: Patient-derived xenograft (PDX) models have shown great promise in preclinical and translational applications, but their consistency with primary tumors in phenotypic, genetic, and pharmacodynamic heterogeneity has not been well-studied. This study aimed to establish a PDX repository for non-small cell lung cancer (NSCLC) and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients. Methods: A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice. Based on the successful establishment of the NSCLC PDX model, we compared the expressions of vimentin, Ki67, EGFR, and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining. In addition, we detected whole gene expression profiling between primary tumors and PDX generations. We also performed whole exome sequencing (WES) analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities. Finally, paclitaxel, cisplatin, doxorubicin, atezolizumab, afatininb, and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents. Results: A large collection of serially transplantable PDX models for NSCLC were successfully developed. The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’ tumor samples. WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors. Similar to clinical patients, PDX models responded differentially to the standard-of-care treatment, including chemo-, targeted- and immuno-therapeutics. Conclusions: Our established PDX models of NSCLC faithfully reproduced the molecular, histopathological, and therapeutic characteristics, as well as the corresponding tumor heterogeneities, which provides a clinically relevant platform for drug screening, biomarker discovery, and translational research.
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- 2021
- Full Text
- View/download PDF
4. Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
- Author
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Qiyi Feng, Junhuai Xu, Xinyi Liu, Haibo Wang, Junjie Xiong, and Kai Xiao
- Subjects
tumor microenvironment ,ph-responsive ,micelles ,β-thiopropionate linkage ,drug delivery ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Stimuli-responsive nanotherapeutics hold great promise in precision oncology. In this study, a facile strategy was used to develop a new class of pH-responsive micelles, which contain methoxy polyethylene glycol (mPEG) and poly(carbobenzoxy-l-glutamic acid, BLG) as amphiphilic copolymer, and β-thiopropionate as acid-labile linkage. The mPEG-S-PBLG copolymer was synthesized through one-step ring-opening polymerization (ROP) and thiol-ene click reaction, and was able to efficiently encapsulate doxorubicin (DOX) to form micelles. The physicochemical characteristics, cellular uptake, tumor targeting, and anti-tumor efficacy of DOX-loaded micelles were investigated. DOX-loaded micelles were stable under physiological conditions and disintegrated under acidic conditions. DOX-loaded micelles can be internalized into cancer cells and release drugs in response to low pH in endosomes/lysosomes, resulting in cell death. Furthermore, the micellar formulation significantly prolonged the blood circulation, reduced the cardiac distribution, and selectively delivered more drugs to tumor tissue. Finally, compared with free DOX, DOX-loaded micelles significantly improved the anti-tumor efficacy and reduced systemic and cardiac toxicity in two different tumor xenograft models. These results suggest that mPEG-S-PBLG micelles have translational potential in the precise delivery of anti-cancer drugs.
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- 2021
- Full Text
- View/download PDF
5. Nanoparticle-Mediated Delivery of STAT3 Inhibitors in the Treatment of Lung Cancer
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Qiyi Feng and Kai Xiao
- Subjects
lung cancer ,STAT3 ,nanoparticles ,drug delivery ,cancer stem cells ,Pharmacy and materia medica ,RS1-441 - Abstract
Lung cancer is a common malignancy worldwide, with high morbidity and mortality. Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor that not only regulates different hallmarks of cancer, such as tumorigenesis, cell proliferation, and metastasis but also regulates the occurrence and maintenance of cancer stem cells (CSCs). Abnormal STAT3 activity has been found in a variety of cancers, including lung cancer, and its phosphorylation level is associated with a poor prognosis of lung cancer. Therefore, the STAT3 pathway may represent a promising therapeutic target for the treatment of lung cancer. To date, various types of STAT3 inhibitors, including natural compounds, small molecules, and gene-based therapies, have been developed through direct and indirect strategies, although most of them are still in the preclinical or early clinical stages. One of the main obstacles to the development of STAT3 inhibitors is the lack of an effective targeted delivery system to improve their bioavailability and tumor targetability, failing to fully demonstrate their anti-tumor effects. In this review, we will summarize the recent advances in STAT3 targeting strategies, as well as the applications of nanoparticle-mediated targeted delivery of STAT3 inhibitors in the treatment of lung cancer.
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- 2022
- Full Text
- View/download PDF
6. Mitochondria-Targeting and Multiresponsive Nanoplatform Based on AIEgens for Synergistic Chemo-Photodynamic Therapy and Enhanced Immunotherapy
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Qiyi Feng, Junhuai Xu, Cheng Zhuang, Junjie Xiong, Haibo Wang, and Kai Xiao
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Biomaterials ,Polymers and Plastics ,Materials Chemistry ,Bioengineering - Published
- 2023
7. SUMOylation facilitates the assembly of a Nuclear Factor‐Y complex to enhance thermotolerance in Arabidopsis
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Junwen Huang, Junjie Huang, Qiyi Feng, Yaqiao Shi, Feige Wang, Kaiyong Zheng, Qize Huang, Jieming Jiang, Siyi Luo, Yun Xie, Danlu Han, Jianbin Lai, and Chengwei Yang
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Plant Science ,Biochemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Heat stress (HS) has serious negative effects on plant development and has become a major threat to agriculture. A rapid transcriptional regulatory cascade has evolved in plants in response to HS. Nuclear Factor-Y (NF-Y) complexes are critical for this mechanism, but how NF-Y complexes are regulated remains unclear. In this study, we identified NF-YC10 (NF-Y subunit C10), a central regulator of the HS response in Arabidopsis thaliana, as a substrate of SUMOylation, an important post-translational modification. Biochemical analysis showed that the SUMO ligase SIZ1 (SAP AND MIZ1 DOMAIN-CONTAINING LIGASE1) interacts with NF-YC10 and enhances its SUMOylation during HS. The SUMOylation of NF-YC10 facilitates its interaction with and the nuclear translocation of NF-YB3, in which the SUMO interaction motif (SIM) is essential for its efficient association with NF-YC10. Further functional analysis indicated that the SUMOylation of NF-YC10 and the SIM of NF-YB3 are critical for HS-responsive gene expression and plant thermotolerance. These findings uncover a role for the SIZ1-mediated SUMOylation of NF-YC10 in NF-Y complex assembly under HS, providing new insights into the role of a post-translational modification in regulating transcription during abiotic stress responses in plants.
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- 2023
8. Nirmatrelvir–ritonavir compared with other antiviral drugs for the treatment of COVID‐19 patients: A systematic review and meta‐analysis
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Fangyuan Tian, Zhaoyan Chen, and Qiyi Feng
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Infectious Diseases ,Virology - Published
- 2023
9. Diversity-oriented synthesis of diterpenoid alkaloids yields a potent anti-inflammatory agent
- Author
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Xiaojie Li, Jifa Zhang, Qifeng Chen, Pan Tang, Ting Zhang, Qiyi Feng, Jiajun Chen, Yun Liu, Feng-Peng Wang, Cheng Peng, Yong Qin, Liang Ouyang, Kai Xiao, and Xiao-Yu Liu
- Subjects
Pharmacology ,Complementary and alternative medicine ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Published
- 2023
10. Efficacy and safety of molnupiravir treatment for COVID-19: a systematic review and meta-analysis of randomized controlled trials
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Fangyuan Tian, Qiyi Feng, and Zhaoyan Chen
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Microbiology (medical) ,Infectious Diseases ,Pharmacology (medical) ,General Medicine - Published
- 2023
11. Patient-derived non-small cell lung cancer xenograft mirrors complex tumor heterogeneity
- Author
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Qiyi Feng, Rui Zhang, Kai Xiao, Guowei Che, Yanjun Xu, Ting Zhang, Yongsheng Wang, Jinxing Huang, Yuanli Zhang, Ke Chen, Cheng Shen, Zhihui Zhong, Xuanming Chen, Shuang Qiu, Bin Chen, Wei Zhe, Lili Jiang, and Hongxia Li
- Subjects
Male ,0301 basic medicine ,endocrine system ,Cancer Research ,Lung Neoplasms ,H&E stain ,non-small cell lung cancer (NSCLC) ,Antineoplastic Agents ,Vimentin ,Mice, SCID ,lcsh:RC254-282 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Mice, Inbred NOD ,Atezolizumab ,Carcinoma, Non-Small-Cell Lung ,tumor heterogeneity ,medicine ,Animals ,Humans ,Lung cancer ,Cisplatin ,non-small cell lung cancer (nsclc) ,biology ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Xenograft Model Antitumor Assays ,Gene expression profiling ,030104 developmental biology ,patient-derived xenograft (pdx) ,Oncology ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Immunohistochemistry ,Female ,Original Article ,Drug Screening Assays, Antitumor ,business ,medicine.drug - Abstract
Objective: Patient-derived xenograft (PDX) models have shown great promise in preclinical and translational applications, but their consistency with primary tumors in phenotypic, genetic, and pharmacodynamic heterogeneity has not been well-studied. This study aimed to establish a PDX repository for non-small cell lung cancer (NSCLC) and to further elucidate whether it could preserve the heterogeneity within and between tumors in patients. Methods: A total of 75 surgically resected NSCLC specimens were implanted into immunodeficient NOD/SCID mice. Based on the successful establishment of the NSCLC PDX model, we compared the expressions of vimentin, Ki67, EGFR, and PD-L1 proteins between cancer tissues and PDX models using hematoxylin and eosin staining and immunohistochemical staining. In addition, we detected whole gene expression profiling between primary tumors and PDX generations. We also performed whole exome sequencing (WES) analysis in 17 first generation xenografts to further assess whether PDXs retained the patient heterogeneities. Finally, paclitaxel, cisplatin, doxorubicin, atezolizumab, afatininb, and AZD4547 were used to evaluate the responses of PDX models to the standard-of-care agents. Results: A large collection of serially transplantable PDX models for NSCLC were successfully developed. The histology and pathological immunohistochemistry of PDX xenografts were consistent with the patients’ tumor samples. WES and RNA-seq further confirmed that PDX accurately replicated the molecular heterogeneities of primary tumors. Similar to clinical patients, PDX models responded differentially to the standard-of-care treatment, including chemo-, targeted- and immuno-therapeutics. Conclusions: Our established PDX models of NSCLC faithfully reproduced the molecular, histopathological, and therapeutic characteristics, as well as the corresponding tumor heterogeneities, which provides a clinically relevant platform for drug screening, biomarker discovery, and translational research.
- Published
- 2021
12. Targeted delivery by pH-responsive mPEG-S-PBLG micelles significantly enhances the anti-tumor efficacy of doxorubicin with reduced cardiotoxicity
- Author
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Kai Xiao, Qiyi Feng, Haibo Wang, Junhuai Xu, Xinyi Liu, and Junjie Xiong
- Subjects
β-thiopropionate linkage ,Cell Survival ,Polymers ,micelles ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,Antineoplastic Agents ,Polyethylene glycol ,RM1-950 ,Micelle ,Polyethylene Glycols ,chemistry.chemical_compound ,Mice ,Cell Line, Tumor ,medicine ,Distribution (pharmacology) ,Animals ,Humans ,tumor microenvironment ,Doxorubicin ,Particle Size ,Precision Medicine ,Cardiotoxicity ,Drug Carriers ,Mice, Inbred BALB C ,Chemistry ,General Medicine ,Hydrogen-Ion Concentration ,Rats ,Drug Liberation ,ph-responsive ,Drug delivery ,Cancer cell ,drug delivery ,Biophysics ,Click chemistry ,Nanoparticles ,Female ,Therapeutics. Pharmacology ,medicine.drug ,Research Article - Abstract
Stimuli-responsive nanotherapeutics hold great promise in precision oncology. In this study, a facile strategy was used to develop a new class of pH-responsive micelles, which contain methoxy polyethylene glycol (mPEG) and poly(carbobenzoxy-l-glutamic acid, BLG) as amphiphilic copolymer, and β-thiopropionate as acid-labile linkage. The mPEG-S-PBLG copolymer was synthesized through one-step ring-opening polymerization (ROP) and thiol-ene click reaction, and was able to efficiently encapsulate doxorubicin (DOX) to form micelles. The physicochemical characteristics, cellular uptake, tumor targeting, and anti-tumor efficacy of DOX-loaded micelles were investigated. DOX-loaded micelles were stable under physiological conditions and disintegrated under acidic conditions. DOX-loaded micelles can be internalized into cancer cells and release drugs in response to low pH in endosomes/lysosomes, resulting in cell death. Furthermore, the micellar formulation significantly prolonged the blood circulation, reduced the cardiac distribution, and selectively delivered more drugs to tumor tissue. Finally, compared with free DOX, DOX-loaded micelles significantly improved the anti-tumor efficacy and reduced systemic and cardiac toxicity in two different tumor xenograft models. These results suggest that mPEG-S-PBLG micelles have translational potential in the precise delivery of anti-cancer drugs.
- Published
- 2021
13. Targeted Drug/Gene/Photodynamic Therapy via a Stimuli‐Responsive Dendritic‐Polymer‐Based Nanococktail for Treatment of EGFR‐TKI‐Resistant Non‐Small‐Cell Lung Cancer
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Jinxing Huang, Cheng Zhuang, Jie Chen, Xuanming Chen, Xiaojie Li, Ting Zhang, Bing Wang, Qiyi Feng, Xiuli Zheng, Meng Gong, Qiyong Gong, Kai Xiao, Kui Luo, and Weimin Li
- Subjects
Lung Neoplasms ,Mechanical Engineering ,Stimuli Responsive Polymers ,Xenograft Model Antitumor Assays ,ErbB Receptors ,Pharmaceutical Preparations ,Photochemotherapy ,Drug Resistance, Neoplasm ,Mechanics of Materials ,Carcinoma, Non-Small-Cell Lung ,Cell Line, Tumor ,Humans ,General Materials Science ,RNA, Small Interfering ,Protein Kinase Inhibitors ,Cell Proliferation - Abstract
Yes-associated protein (YAP) has been identified as a key driver for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance. Inhibition of YAP expression could be a potential therapeutic option for treating non-small-cell lung cancer (NSCLC). Herein, a nanococktail therapeutic strategy is proposed by employing amphiphilic and block-dendritic-polymer-based nanoparticles (NPs) for targeted co-delivery of EGFR-TKI gefitinib (Gef) and YAP-siRNA to achieve a targeted drug/gene/photodynamic therapy. The resulting NPs are effectively internalized into Gef-resistant NSCLC cells, successfully escape from late endosomes/lysosomes, and responsively release Gef and YAP-siRNA in an intracellular reductive environment. They preferentially accumulate at the tumor site after intravenous injection in both cell-line-derived xenograft (CDX) and patient-derived xenograft (PDX) models of Gef-resistant NSCLC, resulting in potent antitumor efficacy without distinct toxicity after laser irradiation. Mechanism studies reveal that the cocktail therapy could block the EGFR signaling pathway with Gef, inhibit activation of the EGFR bypass signaling pathway via YAP-siRNA, and induce tumor cell apoptosis through photodynamic therapy (PDT). Furthermore, this combination nanomedicine can sensitize PDT and impair glycolysis by downregulating HIF-1α. These results suggest that this stimuli-responsive dendritic-polymer-based nanococktail therapy may provide a promising approach for the treatment of EGFR-TKI resistant NSCLC.
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- 2022
14. The effect of particle size on the genotoxicity of gold nanoparticles
- Author
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Ying Liu, Hongxia Li, Qiyue Xia, Shuyang Zhang, Qiyi Feng, and Kai Xiao
- Subjects
0301 basic medicine ,Materials science ,DNA damage ,Metals and Alloys ,Biomedical Engineering ,Nanotechnology ,02 engineering and technology ,021001 nanoscience & nanotechnology ,medicine.disease_cause ,Biomaterials ,Comet assay ,03 medical and health sciences ,Clastogen ,030104 developmental biology ,Colloidal gold ,In vivo ,Micronucleus test ,Ceramics and Composites ,Biophysics ,medicine ,0210 nano-technology ,Micronucleus ,Genotoxicity - Abstract
Despite the increasing biomedical applications of gold nanoparticles (AuNPs), their toxicological effects need to be thoroughly understood. In the present study, the genotoxic potential of commercially available AuNPs with varying size (5, 20, and 50 nm) were assessed using a battery of in vitro and in vivo genotoxicity assays. In the comet assay, 20 and 50 nm AuNPs did not induce obvious DNA damage in HepG2 cells at the tested concentrations, whereas 5 nm NPs induced a dose-dependent increment in DNA damage after 24-h exposure. Furthermore, 5 nm AuNPs induced cell cycle arrest in G1 phase in response to DNA damage, and promoted the production of reactive oxygen species (ROS). In the chromosomal aberration test, AuNPs exposure did not increase in the frequency of chromosomal aberrations in Chinese hamster lung (CHL) cells. In the standard in vivo micronucleus test, no obvious increase in the frequency of micronucleus formation was found in mice after 4 day exposure of AuNPs. However, when the exposure period was extended to 14 days, 5 nm AuNPs presented significant clastogenic damage, with a dose-dependent increase of micronuclei frequencies. This finding suggests that particle size plays an important role in determining the genotoxicity of AuNPs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 710-719, 2017.
- Published
- 2016
15. Multi-Modal Visualization of Uptake and Distribution of Iron Oxide Nanoparticles in Macrophages, Cancer Cells, and Xenograft Models
- Author
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Qiangqiang Liu, Ting Zhang, Qiyi Feng, Xiaojie Li, Kai Xiao, Jinxing Huang, Xuanming Chen, Hongxia Li, Zhihui Zhong, and Xinyi Liu
- Subjects
Endosome ,Confocal ,0206 medical engineering ,Cell ,Endocytic cycle ,Biomedical Engineering ,Pharmaceutical Science ,Medicine (miscellaneous) ,Bioengineering ,02 engineering and technology ,Endocytosis ,Ferric Compounds ,chemistry.chemical_compound ,Mice ,medicine ,Fluorescence microscope ,Animals ,General Materials Science ,Macrophages ,021001 nanoscience & nanotechnology ,020601 biomedical engineering ,medicine.anatomical_structure ,chemistry ,Cancer cell ,Biophysics ,Heterografts ,Nanoparticles ,0210 nano-technology ,Iron oxide nanoparticles - Abstract
Iron oxide nanoparticles (IONPs) have shown great potential in various biomedical applications. However, information on the interaction between IONPs and biological systems, especially the uptake and distribution of IONPs in cells and tissues, as well as the mechanism of biological action, is relatively limited. In the present study, multi-modal visualization methods, including confocal fluorescence microscopy, transmission electron microscopy, magnetic resonance imaging, and fluorescence optical imaging, were utilized to unveil the uptake and distribution of IONPs in macrophages, cancer cells, and xenograft models. Our results demonstrated that uptake of IONPs in RAW264.7 macrophages and SKOV-3 cancer cells were dose- and cell type-dependent. Cellular uptake of IONPs was an energy-dependent process, and caveolae-mediated endocytosis was the main uptake pathway. All the IONPs were primarily present in endocytic compartments (e.g., endosomes, lysosomes) inside the cells. At 48 hours after intravenous injection of IONPs in SKOV-3 tumor bearing mice, most of the IONPs was distributed in the liver and spleen, with obvious uptake in the tumor, less but significant amount in the kidney and brain. Taken together, multi-modal visualization approaches in our study provide detailed information on the cellular uptake and tissue distribution of IONPs from multiple levels and perspectives.
- Published
- 2019
16. Size- and cell type-dependent cellular uptake, cytotoxicity and in vivo distribution of gold nanoparticles
- Author
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Qiyue, Xia, Jinxing, Huang, Qiyi, Feng, Xuanming, Chen, Xinyi, Liu, Xiaojie, Li, Ting, Zhang, Shuwen, Xiao, Hongxia, Li, Zhihui, Zhong, and Kai, Xiao
- Subjects
Mice, Inbred BALB C ,Caspase 3 ,Metal Nanoparticles ,toxicity ,Apoptosis ,Hep G2 Cells ,particle size ,Hemolysis ,Mice ,gold nanoparticles ,uptake ,Toxicity Tests ,Animals ,Cytokines ,Humans ,Tissue Distribution ,Gold ,Reactive Oxygen Species ,biodistribution ,Original Research - Abstract
Background Gold nanoparticles (AuNPs) have shown great promise in biomedical applications. However, the interaction of AuNPs with biological systems, its underlying mechanisms and influencing factors need to be further elucidated. Purpose The aim of this study was to systematically investigate the effects of particle size on the uptake and cytotoxicity of AuNPs in normal cells and cancer cells as well as their biological distribution in vivo. Results Our data demonstrated that the uptake of AuNPs increased in HepG2 cancer cells but decreased in L02 normal cells, with the increase of particle size (5-50 nm). In both cancer cells and normal cells, small (5 nm) AuNPs exhibited greater cytotoxicity than large ones (20 and 50 nm). Interestingly, 5 nm AuNPs induced both apoptosis and necrosis in HepG2 cells through the production of reactive oxygen species (ROS) and the activation of pro-caspase3, whereas it mainly induced necrosis in L02 cells through the overexpression of TLR2 and the release of IL-6 and IL-1a cytokines. Among them, 50 nm AuNPs showed the longest blood circulation and highest distribution in liver and spleen, and the treatment of 5 nm AuNPs but not 20 nm and 50 nm AuNPs resulted in the increase of neutrophils and slight hepatotoxicity in mice. Conclusion Our results indicate that the particle size of AuNPs and target cell type are critical determinants of cellular uptake, cytotoxicity and underlying mechanisms, and biological distribution in vivo, which deserves careful consideration in the future biomedical applications.
- Published
- 2019
17. Uptake, distribution, clearance, and toxicity of iron oxide nanoparticles with different sizes and coatings
- Author
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Jian Huang, Qiyi Feng, Jinxing Huang, Kai Xiao, Yanping Liu, and Ke Chen
- Subjects
Biodistribution ,lcsh:Medicine ,Metal Nanoparticles ,Mice, Nude ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Ferric Compounds ,Article ,Cell Line ,Polyethylene Glycols ,chemistry.chemical_compound ,Mice ,In vivo ,Cell Line, Tumor ,Autophagy ,Distribution (pharmacology) ,Animals ,Humans ,Polyethyleneimine ,Tissue Distribution ,lcsh:Science ,Cytotoxicity ,Polyethylenimine ,Mice, Inbred BALB C ,Multidisciplinary ,Chemistry ,lcsh:R ,021001 nanoscience & nanotechnology ,In vitro ,0104 chemical sciences ,Toxicity ,Inactivation, Metabolic ,Biophysics ,lcsh:Q ,Female ,0210 nano-technology ,Iron oxide nanoparticles - Abstract
Iron oxide nanoparticles (IONPs) have been increasingly used in biomedical applications, but the comprehensive understanding of their interactions with biological systems is relatively limited. In this study, we systematically investigated the in vitro cell uptake, cytotoxicity, in vivo distribution, clearance and toxicity of commercially available and well-characterized IONPs with different sizes and coatings. Polyethylenimine (PEI)-coated IONPs exhibited significantly higher uptake than PEGylated ones in both macrophages and cancer cells, and caused severe cytotoxicity through multiple mechanisms such as ROS production and apoptosis. 10 nm PEGylated IONPs showed higher cellular uptake than 30 nm ones, and were slightly cytotoxic only at high concentrations. Interestingly, PEGylated IONPs but not PEI-coated IONPs were able to induce autophagy, which may play a protective role against the cytotoxicity of IONPs. Biodistribution studies demonstrated that all the IONPs tended to distribute in the liver and spleen, and the biodegradation and clearance of PEGylated IONPs in these tissues were relatively slow (>2 weeks). Among them, 10 nm PEGylated IONPs achieved the highest tumor uptake. No obvious toxicity was found for PEGylated IONPs in BALB/c mice, whereas PEI-coated IONPs exhibited dose-dependent lethal toxicity. Therefore, it is crucial to consider the size and coating properties of IONPs in their applications.
- Published
- 2017
18. The effect of particle size on the genotoxicity of gold nanoparticles
- Author
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Qiyue, Xia, Hongxia, Li, Ying, Liu, Shuyang, Zhang, Qiyi, Feng, and Kai, Xiao
- Subjects
Mice ,Time Factors ,Dose-Response Relationship, Drug ,Animals ,Humans ,Metal Nanoparticles ,Gold ,Hep G2 Cells ,Particle Size ,G1 Phase Cell Cycle Checkpoints ,Micronuclei, Chromosome-Defective ,DNA Damage - Abstract
Despite the increasing biomedical applications of gold nanoparticles (AuNPs), their toxicological effects need to be thoroughly understood. In the present study, the genotoxic potential of commercially available AuNPs with varying size (5, 20, and 50 nm) were assessed using a battery of in vitro and in vivo genotoxicity assays. In the comet assay, 20 and 50 nm AuNPs did not induce obvious DNA damage in HepG2 cells at the tested concentrations, whereas 5 nm NPs induced a dose-dependent increment in DNA damage after 24-h exposure. Furthermore, 5 nm AuNPs induced cell cycle arrest in G1 phase in response to DNA damage, and promoted the production of reactive oxygen species (ROS). In the chromosomal aberration test, AuNPs exposure did not increase in the frequency of chromosomal aberrations in Chinese hamster lung (CHL) cells. In the standard in vivo micronucleus test, no obvious increase in the frequency of micronucleus formation was found in mice after 4 day exposure of AuNPs. However, when the exposure period was extended to 14 days, 5 nm AuNPs presented significant clastogenic damage, with a dose-dependent increase of micronuclei frequencies. This finding suggests that particle size plays an important role in determining the genotoxicity of AuNPs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 710-719, 2017.
- Published
- 2016
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