Pub Date : 2024-11-03eCollection Date: 2024-01-01DOI: 10.2147/IJN.S486827
Iris Xiaoxue Yin, John Yun Niu, May Lei Mei, Jinyao Tang, William Ka Kei Wu, Chun Hung Chu
Objective: The objectives of this study were to develop a tooth-binding graphene quantum dots silver nanocomposites (ALN-GQDs-Ag) and evaluate their antibacterial, mineralising, and discolouring properties for the prevention of dental caries.
Methods: In this study, ALN-GQDs-Ag were developed by synthesising nano silver (Ag) with graphene quantum dots (GQDs) and functionalised GQDs with alendronate (ALN). ALN-GQDs-Ag were characterised by transmission electron microscopy (TEM), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. The cytotoxicity of ALN-GQDs-Ag against human gingival fibroblasts (HGF-1) and stem cells from human exfoliated deciduous teeth (SHED) was examined using a colorimetric assay with reference to silver nitrate solution. The affinity of ALN-GQDs-Ag for hydroxyapatite particles was investigated using inductively coupled plasma spectroscopy (ICP). The antibacterial properties of ALN-GQDs-Ag against Streptococcus mutans were evaluated by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and colony-forming units counting (CFUs). The mineralisation properties of ALN-GQDs-Ag on human dentine were assessed using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), and Fourier transform infrared in a biochemical cycling model. The discolouring properties of ALN-GQDs-Ag on artificial dentine caries were determined using spectrophotometry.
Results: TEM, Zeta potential, XPS, FTIR, and Raman spectroscopy confirmed the synthesis of stable spherical ALN-GQD-Ag nanocomposites with a 10.3 ± 5.5 nm diameter. The colorimetric assay demonstrated that ALN-GQDs-Ag were less cytotoxic than silver nitrate to HGF-1 and SHED (p<0.001). ICP showed that ALN-GQDs-Ag were bound to hydroxyapatite. SEM, CLSM, and CFUs showed that ALN-GQDs-Ag was bactericidal and inhibited biofilm growth of Streptococcus mutans. Micro-CT, SEM, and FTIR showed that ALN-GQDs-Ag repressed dentine demineralisation under a cariogenic challenge. Spectrophotometry revealed no significant discolouration of dentine caries in the ALN-GQDs-Ag.
Conclusion: This study developed a biocompatible and tooth-binding ALN-GQDs-Ag with promising antibacterial, mineralising, and non-discolouring properties. ALN-GQDs-Ag could be a novel anti-caries agent for preventing dentine caries if translated for clinical use.
{"title":"Tooth-Binding Graphene Quantum Dots Silver Nanocomposites for Prevention of Dental Caries.","authors":"Iris Xiaoxue Yin, John Yun Niu, May Lei Mei, Jinyao Tang, William Ka Kei Wu, Chun Hung Chu","doi":"10.2147/IJN.S486827","DOIUrl":"https://doi.org/10.2147/IJN.S486827","url":null,"abstract":"<p><strong>Objective: </strong>The objectives of this study were to develop a tooth-binding graphene quantum dots silver nanocomposites (ALN-GQDs-Ag) and evaluate their antibacterial, mineralising, and discolouring properties for the prevention of dental caries.</p><p><strong>Methods: </strong>In this study, ALN-GQDs-Ag were developed by synthesising nano silver (Ag) with graphene quantum dots (GQDs) and functionalised GQDs with alendronate (ALN). ALN-GQDs-Ag were characterised by transmission electron microscopy (TEM), zeta potential analysis, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy. The cytotoxicity of ALN-GQDs-Ag against human gingival fibroblasts (HGF-1) and stem cells from human exfoliated deciduous teeth (SHED) was examined using a colorimetric assay with reference to silver nitrate solution. The affinity of ALN-GQDs-Ag for hydroxyapatite particles was investigated using inductively coupled plasma spectroscopy (ICP). The antibacterial properties of ALN-GQDs-Ag against <i>Streptococcus mutans</i> were evaluated by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and colony-forming units counting (CFUs). The mineralisation properties of ALN-GQDs-Ag on human dentine were assessed using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), and Fourier transform infrared in a biochemical cycling model. The discolouring properties of ALN-GQDs-Ag on artificial dentine caries were determined using spectrophotometry.</p><p><strong>Results: </strong>TEM, Zeta potential, XPS, FTIR, and Raman spectroscopy confirmed the synthesis of stable spherical ALN-GQD-Ag nanocomposites with a 10.3 ± 5.5 nm diameter. The colorimetric assay demonstrated that ALN-GQDs-Ag were less cytotoxic than silver nitrate to HGF-1 and SHED (p<0.001). ICP showed that ALN-GQDs-Ag were bound to hydroxyapatite. SEM, CLSM, and CFUs showed that ALN-GQDs-Ag was bactericidal and inhibited biofilm growth of <i>Streptococcus mutans</i>. Micro-CT, SEM, and FTIR showed that ALN-GQDs-Ag repressed dentine demineralisation under a cariogenic challenge. Spectrophotometry revealed no significant discolouration of dentine caries in the ALN-GQDs-Ag.</p><p><strong>Conclusion: </strong>This study developed a biocompatible and tooth-binding ALN-GQDs-Ag with promising antibacterial, mineralising, and non-discolouring properties. ALN-GQDs-Ag could be a novel anti-caries agent for preventing dentine caries if translated for clinical use.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11195-11212"},"PeriodicalIF":6.6,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Burn wounds pose intricate clinical challenges due to their severity and high risk of complications, demanding advanced therapeutic strategies beyond conventional treatments. This review discusses the application of nanoparticle-based therapies for optimizing burn wound healing. We explore the critical phases of burn wound healing, including inflammation, proliferation, and remodeling, while summarizing key nanoparticle-based strategies that influence these processes to optimize healing. Various nanoparticles, such as metal-based, polymer-based, and extracellular vesicles, are evaluated for their distinctive properties and mechanisms of action, including antimicrobial, anti-inflammatory, and regenerative effects. Future directions are highlighted, focusing on personalized therapies and the integration of sophisticated drug delivery systems, emphasizing the transformative potential of nanoparticles in enhancing burn wound treatment.
{"title":"Nanoparticle-Based Therapeutics for Enhanced Burn Wound Healing: A Comprehensive Review.","authors":"Shaoyan Shi, Xuehai Ou, Jiafeng Long, Xiqin Lu, Siqi Xu, Li Zhang","doi":"10.2147/IJN.S490027","DOIUrl":"https://doi.org/10.2147/IJN.S490027","url":null,"abstract":"<p><p>Burn wounds pose intricate clinical challenges due to their severity and high risk of complications, demanding advanced therapeutic strategies beyond conventional treatments. This review discusses the application of nanoparticle-based therapies for optimizing burn wound healing. We explore the critical phases of burn wound healing, including inflammation, proliferation, and remodeling, while summarizing key nanoparticle-based strategies that influence these processes to optimize healing. Various nanoparticles, such as metal-based, polymer-based, and extracellular vesicles, are evaluated for their distinctive properties and mechanisms of action, including antimicrobial, anti-inflammatory, and regenerative effects. Future directions are highlighted, focusing on personalized therapies and the integration of sophisticated drug delivery systems, emphasizing the transformative potential of nanoparticles in enhancing burn wound treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11213-11233"},"PeriodicalIF":6.6,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Eprinomectin offers promise against parasitic infections. This study develops Eprinomectin (EPR) mixed micelles for transdermal delivery, aiming to enhance efficacy and convenience against endoparasites and ectoparasites. Physicochemical characterization and pharmacokinetic studies were conducted to assess its potential as an effective treatment for parasitic infections.
Methods: Blank and EPR mixed micelles were prepared using PEG-40 Hydrogenated castor oil (RH-40) and Nonyl phenol polyoxyethylene ether 40 (NP-40). Critical micelle concentrations (CMC) determined using the pyrene fluorescence probe method. Particle size, EE, DL, in vitro release, permeation, and skin irritation were evaluated. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley rats.
Results: Results show that EPR mixed micelles present suitable stability, physicochemical properties, and safety. Moreover, the rapid release and high bioavailability of EPR mixed micelles have also been verified in the study. Pharmacokinetic experiments in vivo showed that an improvement in the transdermal absorption and bioavailability of EPR after encapsulation in mixed micelles formulations.
Conclusion: The results proved that the novel mixed micelles are safe and effective and are expected to become a promising veterinary nano-delivery system.
{"title":"Penetration Enhancer-Free Mixed Micelles for Improving Eprinomectin Transdermal c Efficiency in Animal Parasitic Infections Therapy.","authors":"Yujuan Mao, Tianjiao Hao, Hongxiu Zhang, Xiaofei Gu, Jing Wang, Feifei Shi, Xiaolan Chen, Liuna Guo, Jie Gao, Yan Shen, JinLin Zhang, Shenglan Yu","doi":"10.2147/IJN.S476164","DOIUrl":"10.2147/IJN.S476164","url":null,"abstract":"<p><strong>Introduction: </strong>Eprinomectin offers promise against parasitic infections. This study develops Eprinomectin (EPR) mixed micelles for transdermal delivery, aiming to enhance efficacy and convenience against endoparasites and ectoparasites. Physicochemical characterization and pharmacokinetic studies were conducted to assess its potential as an effective treatment for parasitic infections.</p><p><strong>Methods: </strong>Blank and EPR mixed micelles were prepared using PEG-40 Hydrogenated castor oil (RH-40) and Nonyl phenol polyoxyethylene ether 40 (NP-40). Critical micelle concentrations (CMC) determined using the pyrene fluorescence probe method. Particle size, EE, DL, in vitro release, permeation, and skin irritation were evaluated. In vivo pharmacokinetic studies were conducted in male Sprague-Dawley rats.</p><p><strong>Results: </strong>Results show that EPR mixed micelles present suitable stability, physicochemical properties, and safety. Moreover, the rapid release and high bioavailability of EPR mixed micelles have also been verified in the study. Pharmacokinetic experiments in vivo showed that an improvement in the transdermal absorption and bioavailability of EPR after encapsulation in mixed micelles formulations.</p><p><strong>Conclusion: </strong>The results proved that the novel mixed micelles are safe and effective and are expected to become a promising veterinary nano-delivery system.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11071-11085"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01eCollection Date: 2024-01-01DOI: 10.2147/IJN.S472796
Meng Xiang, Chengzhi Chen, Yuting Chen, Yuhan Zhang, Lei Shi, Yan Chen, Jie Li, Bowen Li, Bin Zeng, H Rosie Xing, Jianyu Wang, Zhen Zou
Introduction: Inhalation exposure to silica nanoparticles (SiNPs) is frequently inevitable in modern times. Although the impact of SiNPs on the ecological niche of the lungs has been extensively explored, the role and mechanism of SiNPs in the microenvironment of lung tumors remain elusive.
Methods: In this investigation, Lewis lung carcinoma (LLC) was implanted into the left lung in situ after 28 days of intratracheal SiNPs injection into the lungs of mice. This study evaluates the effects of SiNPs on the tumor immune microenvironment both in vitro and in vivo. Our findings indicate that SiNPs can suppress lung cancer by modulating the immune microenvironment of tumors.
Results: SiNPs treatment promotes macrophage M1 polarization by activating both NF-κB pathway and glycolytic mechanisms. This phenomenon may be associated with lung inflammation and fluctuation in the pre-metastatic and metastatic microenvironments induced by SiNPs exposure in mice. Additionally, we have shown for the first time that SiNPs have an inhibitory effect on lung carcinogenesis and its progression.
Conclusion: This study uniquely demonstrates that SiNPs suppress lung cancer by promoting M1 polarization of macrophages in the immune microenvironment of lung tumors. Our findings are critical in exploring the interaction between SiNPs and lung cancer.
{"title":"Unexpected Inhibitory Role of Silica Nanoparticles on Lung Cancer Development by Promoting M1 Polarization of Macrophages.","authors":"Meng Xiang, Chengzhi Chen, Yuting Chen, Yuhan Zhang, Lei Shi, Yan Chen, Jie Li, Bowen Li, Bin Zeng, H Rosie Xing, Jianyu Wang, Zhen Zou","doi":"10.2147/IJN.S472796","DOIUrl":"10.2147/IJN.S472796","url":null,"abstract":"<p><strong>Introduction: </strong>Inhalation exposure to silica nanoparticles (SiNPs) is frequently inevitable in modern times. Although the impact of SiNPs on the ecological niche of the lungs has been extensively explored, the role and mechanism of SiNPs in the microenvironment of lung tumors remain elusive.</p><p><strong>Methods: </strong>In this investigation, Lewis lung carcinoma (LLC) was implanted into the left lung in situ after 28 days of intratracheal SiNPs injection into the lungs of mice. This study evaluates the effects of SiNPs on the tumor immune microenvironment both in vitro and in vivo. Our findings indicate that SiNPs can suppress lung cancer by modulating the immune microenvironment of tumors.</p><p><strong>Results: </strong>SiNPs treatment promotes macrophage M1 polarization by activating both NF-κB pathway and glycolytic mechanisms. This phenomenon may be associated with lung inflammation and fluctuation in the pre-metastatic and metastatic microenvironments induced by SiNPs exposure in mice. Additionally, we have shown for the first time that SiNPs have an inhibitory effect on lung carcinogenesis and its progression.</p><p><strong>Conclusion: </strong>This study uniquely demonstrates that SiNPs suppress lung cancer by promoting M1 polarization of macrophages in the immune microenvironment of lung tumors. Our findings are critical in exploring the interaction between SiNPs and lung cancer.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11087-11104"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose: The study was intended to compare the surface properties and the bacterial and biofilm adhesion resistance of two potential antibacterial nanometer titanium dioxide (nano-TiO2) coatings on dental titanium (Ti) abutments prepared by atomic layer deposition (ALD) and the anodic oxidation (AO) techniques.
Methods: Nano-TiO₂ coatings were developed using ALD and AO techniques and applied to Ti surfaces. The surface properties and the bacterial and biofilm adhesion resistance of these coatings were evaluated against commonly used Ti and Zirconia (ZrO₂) surfaces. The chemical compositions, crystalline forms, surface topography, roughness and hydrophilicity were characterized. The antibacterial performance was assessed by the scanning electron microscope (SEM), the Colony-forming unit (CFU) assay and the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay using in vitro models of Staphylococcus aureus (S.aureus), Streptococcus mutans (S.mutans), and Porphyromonas gingivalis (P.gingivalis) in both single- and mixed-species bacterial compositions.
Results: ALD-prepared nano-TiO₂ coatings resulted in a dense, smooth, and less hydrophilic surface with an anatase phase, significantly reducing the adhesion of the three bacteria by over 50%, comparable to ZrO₂. In contrast, AO-prepared coatings led to a less hydrophilic surface, characterized by various nano-sized pores within the oxide film. This alteration, however, had no impact on the adhesion of the three bacteria. The adhesion patterns for mixed-species bacteria were generally consistent with single-species results.
Conclusion: ALD-prepared nano-TiO₂ coatings on Ti abutments demonstrated promising antibacterial properties comparable to ZrO₂ surfaces, suggesting potential in preventing peri-implantitis. However, the bacterial and biofilm adhesion resistance of AO-produced nano-TiO₂ coatings was limited.
{"title":"Enhanced Bacterial and Biofilm Adhesion Resistance of ALD Nano-TiO<sub>2</sub> Coatings Compared to AO Coatings on Titanium Abutments.","authors":"Yu Pan, Lili Cao, Libing Chen, Linjuan Gao, Xia Wei, Honglei Lin, Lei Jiang, Yinghui Wang, Hui Cheng","doi":"10.2147/IJN.S482478","DOIUrl":"10.2147/IJN.S482478","url":null,"abstract":"<p><strong>Purpose: </strong>The study was intended to compare the surface properties and the bacterial and biofilm adhesion resistance of two potential antibacterial nanometer titanium dioxide (nano-TiO<sub>2</sub>) coatings on dental titanium (Ti) abutments prepared by atomic layer deposition (ALD) and the anodic oxidation (AO) techniques.</p><p><strong>Methods: </strong>Nano-TiO₂ coatings were developed using ALD and AO techniques and applied to Ti surfaces. The surface properties and the bacterial and biofilm adhesion resistance of these coatings were evaluated against commonly used Ti and Zirconia (ZrO₂) surfaces. The chemical compositions, crystalline forms, surface topography, roughness and hydrophilicity were characterized. The antibacterial performance was assessed by the scanning electron microscope (SEM), the Colony-forming unit (CFU) assay and the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay using in vitro models of <i>Staphylococcus aureus</i> (<i>S.</i> <i>aureus</i>), <i>Streptococcus mutans</i> (<i>S.</i> <i>mutans</i>), and <i>Porphyromonas gingivalis</i> (<i>P.</i> <i>gingivalis</i>) in both single- and mixed-species bacterial compositions.</p><p><strong>Results: </strong>ALD-prepared nano-TiO₂ coatings resulted in a dense, smooth, and less hydrophilic surface with an anatase phase, significantly reducing the adhesion of the three bacteria by over 50%, comparable to ZrO₂. In contrast, AO-prepared coatings led to a less hydrophilic surface, characterized by various nano-sized pores within the oxide film. This alteration, however, had no impact on the adhesion of the three bacteria. The adhesion patterns for mixed-species bacteria were generally consistent with single-species results.</p><p><strong>Conclusion: </strong>ALD-prepared nano-TiO₂ coatings on Ti abutments demonstrated promising antibacterial properties comparable to ZrO₂ surfaces, suggesting potential in preventing peri-implantitis. However, the bacterial and biofilm adhesion resistance of AO-produced nano-TiO₂ coatings was limited.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11143-11159"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01eCollection Date: 2024-01-01DOI: 10.2147/IJN.S480716
Rana Ahmed El-Fitiany, Afra AlBlooshi, Abdelouahid Samadi, Mohammad A Khasawneh
Introduction: Phyto-nanotechnology offers a sustainable method for synthesizing biocompatible metal nanoparticles (NPs) with therapeutic potential. The diverse medicinal flora in the UAE, particularly Leptadenia pyrotechnica (LP), provides a vital resource for advancing this research area. This plant is historically valued in the region for its wide medicinal applications due to its abundance of bioactive compounds.
Methods: In this study, eco-friendly, straightforward, and low-temperature hydrothermal synthesis methods were applied to synthesize potentially therapeutic Zn and Fe NPs using LP extracts. The generated NPs were characterized using UV-VIS, FT-IR, SEM, EDX, XRD and DLS. Moreover, they were investigated for their total phenolic and flavonoid contents, along with their antioxidant and skin anticancer effects.
Results: The UV-Vis spectra disclosed absorption band at about 275 nm, and the FT-IR confirmed the successful coating of the NPs with the plants' phytochemicals, thus ensuring the successful bio-fabrication of the proposed NPs. SEM/EDX outcomes suggest a more potent reducing effect of the aqueous extract, while a more effective coating of the alcoholic extract. DLS revealed monodispersed NPs, with average sizes ranging from 43.82 to 207.8 nm. LFeC demonstrated the highest phenolic and flavonoid contents (49.96±4.76 μg of GAE/mg of DW and 43.89±2.89 μg of Qu/mg of DW, respectively) and the greatest potency against skin cancer cell lines (IC50=263.56 µg/mL). However, LZnC exhibited the strongest radical scavenging effect against DPPH and ABTS radicals (IC50=139.45µg/mL and 35.1µg/mL, respectively).
Discussion: The results of this study demonstrated that both extracts of LP are effective in the green synthesis of Fe and Zn nanoparticles for biomedical applications, with alcoholic extracts providing superior coating, capping, and stabilizing properties, leading to lower agglomeration, higher carbon content, total phenolic and flavonoid contents, along with enhanced anticancer and antioxidant effects. This work gives a showcase of sustainable materials that are promising for therapeutic applications.
{"title":"Phytosynthesis, Characterization, Phenolic and Biological Evaluation of <i>Leptadenia pyrotechnica</i>-Based Zn and Fe Nanoparticles Utilizing Two Different Extraction Techniques.","authors":"Rana Ahmed El-Fitiany, Afra AlBlooshi, Abdelouahid Samadi, Mohammad A Khasawneh","doi":"10.2147/IJN.S480716","DOIUrl":"10.2147/IJN.S480716","url":null,"abstract":"<p><strong>Introduction: </strong>Phyto-nanotechnology offers a sustainable method for synthesizing biocompatible metal nanoparticles (NPs) with therapeutic potential. The diverse medicinal flora in the UAE, particularly <i>Leptadenia pyrotechnica</i> (LP), provides a vital resource for advancing this research area. This plant is historically valued in the region for its wide medicinal applications due to its abundance of bioactive compounds.</p><p><strong>Methods: </strong>In this study, eco-friendly, straightforward, and low-temperature hydrothermal synthesis methods were applied to synthesize potentially therapeutic Zn and Fe NPs using LP extracts. The generated NPs were characterized using UV-VIS, FT-IR, SEM, EDX, XRD and DLS. Moreover, they were investigated for their total phenolic and flavonoid contents, along with their antioxidant and skin anticancer effects.</p><p><strong>Results: </strong>The UV-Vis spectra disclosed absorption band at about 275 nm, and the FT-IR confirmed the successful coating of the NPs with the plants' phytochemicals, thus ensuring the successful bio-fabrication of the proposed NPs. SEM/EDX outcomes suggest a more potent reducing effect of the aqueous extract, while a more effective coating of the alcoholic extract. DLS revealed monodispersed NPs, with average sizes ranging from 43.82 to 207.8 nm. LFeC demonstrated the highest phenolic and flavonoid contents (49.96±4.76 μg of GAE/mg of DW and 43.89±2.89 μg of Qu/mg of DW, respectively) and the greatest potency against skin cancer cell lines (IC<sub>50</sub>=263.56 µg/mL). However, LZnC exhibited the strongest radical scavenging effect against DPPH and ABTS radicals (IC<sub>50</sub>=139.45µg/mL and 35.1µg/mL, respectively).</p><p><strong>Discussion: </strong>The results of this study demonstrated that both extracts of LP are effective in the green synthesis of Fe and Zn nanoparticles for biomedical applications, with alcoholic extracts providing superior coating, capping, and stabilizing properties, leading to lower agglomeration, higher carbon content, total phenolic and flavonoid contents, along with enhanced anticancer and antioxidant effects. This work gives a showcase of sustainable materials that are promising for therapeutic applications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11003-11021"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability.
Purpose: To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability.
Methods: Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Draize corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by Minimal inhibit concentration (MIC), crystal violet staining, Propidium Iodide (PI) testing, and calcofluor white staining. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU), Hematoxylin-eosin (HE) staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis.
Results: In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of Aspergillus fumigatus over 90% at 64 μg/mL, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β after Aspergillus fumigatus infection in vivo and in vitro.
Conclusion: ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis.
{"title":"Zeolitic Imidazolate Framework-8 Offers an Anti-Inflammatory and Antifungal Method in the Treatment of <i>Aspergillus Fungal</i> Keratitis in vitro and in vivo.","authors":"Xueyun Fu, Xue Tian, Jing Lin, Qian Wang, Lingwen Gu, Ziyi Wang, Menghui Chi, Bing Yu, Zhuhui Feng, Wenyao Liu, Lina Zhang, Cui Li, Guiqiu Zhao","doi":"10.2147/IJN.S480800","DOIUrl":"10.2147/IJN.S480800","url":null,"abstract":"<p><strong>Background: </strong>Fungal keratitis is a serious blinding eye disease. Traditional drugs used to treat fungal keratitis commonly have the disadvantages of low bioavailability, poor dispersion, and limited permeability.</p><p><strong>Purpose: </strong>To develop a new method for the treatment of fungal keratitis with improved bioavailability, dispersion, and permeability.</p><p><strong>Methods: </strong>Zeolitic Imidazolate Framework-8 (ZIF-8) was formed by zinc ions and 2-methylimidazole linked by coordination bonds and characterized by Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Zeta potential. The safety of ZIF-8 on HCECs and RAW 264.7 cells was detected by Cell Counting Kit-8 (CCK-8). Safety evaluation of ZIF-8 on mice corneal epithelium was conducted using the Draize corneal toxicity test. The effects of ZIF-8 on fungal growth, biofilm formation, and hyphae structure were detected by Minimal inhibit concentration (MIC), crystal violet staining, Propidium Iodide (PI) testing, and calcofluor white staining. The anti-inflammatory effects of ZIF-8 on RAW 246.7 cells were evaluated by Quantitative Real-Time PCR Experiments (qPCR) and Enzyme-linked immunosorbent assay (ELISA). Clinical score, Colony-Forming Units (CFU), Hematoxylin-eosin (HE) staining, and immunofluorescence were conducted to verify the therapeutic effect of ZIF-8 on C57BL/6 female mice with fungal keratitis.</p><p><strong>Results: </strong>In vitro, ZIF-8 showed outstanding antifungal effects, including inhibiting the growth of <i>Aspergillus fumigatus</i> over 90% at 64 μg/mL, restraining the formation of biofilm, and destroying cell membranes. In vivo, treatment with ZIF-8 reduced corneal fungal load and mitigated neutrophil infiltration in fungal keratitis, which effectively reduced the severity of keratitis in mice and alleviated the infiltration of inflammatory factors in the mouse cornea. In addition, ZIF-8 reduces the inflammatory response by downregulating the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β after <i>Aspergillus fumigatus</i> infection in vivo and in vitro.</p><p><strong>Conclusion: </strong>ZIF-8 has a significant anti-inflammatory and antifungal effect, which provides a new solution for the treatment of fungal keratitis.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11163-11179"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01eCollection Date: 2024-01-01DOI: 10.2147/IJN.S486014
Sheeja S Rajan, Rahul Chandran, Heidi Abrahamse
Hypocrellin-based photodynamic therapy (PDT) is developing as a viable cancer therapeutic option, especially when enhanced by nanoconjugation. This review investigates the methods by which nano-conjugated hypocrellin enhances therapeutic efficacy and precision when targeting cancer cells. These nanoconjugates encapsulate or covalently bind hypocrellin photosensitizers (PSs), allowing them to accumulate preferentially in malignancies. When activated by light, the nanoconjugates produce singlet oxygen and other reactive oxygen species (ROS), resulting in oxidative stress that selectively destroys cancer cells while protecting healthy tissues. We look at how they can be used to treat a variety of cancers. Clinical and preclinical studies show that they have advantages such as increased water solubility, improved tumor penetration, longer circulation times, and tailored delivery, all of which contribute to fewer off-target effects and overall toxicity. Ongoing research focuses on improving these nanoconjugates for better tumor targeting, drug release kinetics, and overcoming biological obstacles. Furthermore, the incorporation of developing technologies such as stimuli-responsive nanocarriers and combination therapies opens exciting opportunities for enhancing hypocrellin-based PDT. In conclusion, the combination of hypocrellin and nanotechnology constitutes a significant approach to cancer treatment, increasing the efficacy and safety of PDT. Future research will seek to create conjugates including hypocrellin, herceptin, and gold nanoparticles to induce apoptosis in human breast cancer cells in vitro, opening possibilities for therapeutic applications.
{"title":"Advancing Photodynamic Therapy with Nano-Conjugated Hypocrellin: Mechanisms and Clinical Applications.","authors":"Sheeja S Rajan, Rahul Chandran, Heidi Abrahamse","doi":"10.2147/IJN.S486014","DOIUrl":"10.2147/IJN.S486014","url":null,"abstract":"<p><p>Hypocrellin-based photodynamic therapy (PDT) is developing as a viable cancer therapeutic option, especially when enhanced by nanoconjugation. This review investigates the methods by which nano-conjugated hypocrellin enhances therapeutic efficacy and precision when targeting cancer cells. These nanoconjugates encapsulate or covalently bind hypocrellin photosensitizers (PSs), allowing them to accumulate preferentially in malignancies. When activated by light, the nanoconjugates produce singlet oxygen and other reactive oxygen species (ROS), resulting in oxidative stress that selectively destroys cancer cells while protecting healthy tissues. We look at how they can be used to treat a variety of cancers. Clinical and preclinical studies show that they have advantages such as increased water solubility, improved tumor penetration, longer circulation times, and tailored delivery, all of which contribute to fewer off-target effects and overall toxicity. Ongoing research focuses on improving these nanoconjugates for better tumor targeting, drug release kinetics, and overcoming biological obstacles. Furthermore, the incorporation of developing technologies such as stimuli-responsive nanocarriers and combination therapies opens exciting opportunities for enhancing hypocrellin-based PDT. In conclusion, the combination of hypocrellin and nanotechnology constitutes a significant approach to cancer treatment, increasing the efficacy and safety of PDT. Future research will seek to create conjugates including hypocrellin, herceptin, and gold nanoparticles to induce apoptosis in human breast cancer cells in vitro, opening possibilities for therapeutic applications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11023-11038"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01eCollection Date: 2024-01-01DOI: 10.2147/IJN.S474098
Lijuan Chen, Mingbo Liu, Yunjuan Wang, Wei Wei, Yaqiong Li, Yan Bai, Xuan Yu, Lei Jiao, Meiyun Wang
Purpose: Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy.
Results: To address these limitations, we developed a highly stable and efficient nanoplatform (MnO2/Pt@BSA). Compared to MnO2@BSA, this platform demonstrates high stability, a high yield of oxygen (O2), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O2 production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO2, the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO2/Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn2+, which serves as a magnetic resonance imaging (MRI) contrast agent with a T1-weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO2/Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM.
Conclusion: This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment.
{"title":"TME-Activated MnO<sub>2</sub>/Pt Nanoplatform of Hydroxyl Radical and Oxygen Generation to Synergistically Promote Radiotherapy and MR Imaging of Glioblastoma.","authors":"Lijuan Chen, Mingbo Liu, Yunjuan Wang, Wei Wei, Yaqiong Li, Yan Bai, Xuan Yu, Lei Jiao, Meiyun Wang","doi":"10.2147/IJN.S474098","DOIUrl":"10.2147/IJN.S474098","url":null,"abstract":"<p><strong>Purpose: </strong>Radiotherapy (RT) is currently recognized as an important treatment for glioblastoma (GBM), however, it is associated with several challenges. One of these challenges is the radioresistance caused by hypoxia, whereas the other is the low conversion efficiency of the strongly oxidized hydroxyl radical (•OH), which is produced by the decomposition of water due to high-energy X-ray radiation. These factors significantly limit the clinical effectiveness of radiotherapy.</p><p><strong>Results: </strong>To address these limitations, we developed a highly stable and efficient nanoplatform (MnO<sub>2</sub>/Pt@BSA). Compared to MnO<sub>2</sub>@BSA, this platform demonstrates high stability, a high yield of oxygen (O<sub>2</sub>), enhanced production of •OH, and reduced clearance of •OH. The system exhibited increased O<sub>2</sub> production in vitro and significantly improved oxygen production efficiency within 100 s at the Pt loading of 38.7%. Furthermore, compared with MnO<sub>2</sub>, the expression rate of hypoxia-inducible factor (HIF-1α) in glioma cells treated with MnO<sub>2</sub>/Pt decreased by half. Additionally, the system promotes •OH generation and consumes glutathione (GSH), thereby inhibiting the clearance of •OH and enhancing its therapeutic effect. Moreover, the degradation of the nanoplatform produces Mn<sup>2+</sup>, which serves as a magnetic resonance imaging (MRI) contrast agent with a T<sub>1</sub>-weighted enhancement effect at the tumor site. The nanoplatform exhibited excellent biocompatibility and performed multiple functions related to radiotherapy, with simpler components. In U87 tumor bearing mice model, we utilized MnO<sub>2</sub>/Pt nanocatalysis to enhance the therapeutic effect of radiotherapy on GBM.</p><p><strong>Conclusion: </strong>This approach represents a novel and effective strategy for enhancing radiotherapy in gliomas, thereby advancing the field of catalytic radiotherapy and glioma treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11055-11070"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p><strong>Purpose: </strong>Ferroptosis is a regulated form of cell death characterized by iron-dependent accumulation of associated lipid peroxides (LPO), which can induce cell death when a certain level is reached. However, the extremely complex tumor microenvironment (TME) has the characteristics of antioxidant, even if it induces ferroptosis of tumor cells, its killing effect on tumor cells is still very limited. To solve this problem, we constructed a novel nanomaterials (GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM). We evaluated the anticancer effect of this nanomaterial in inhibiting tumor growth through comprehensive in vitro and in vivo experiments.</p><p><strong>Methods: </strong>We successfully synthesized GOx/EC@Fe<sub>3</sub>O<sub>4</sub> by one-pan synthesis method, then coated the Hepatocellular carcinoma cell membrane on its surface by co-extrusion technology, and finally synthesized the GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms. We characterized the compounds in terms of morphology, particle size, and Zeta potential. In addition, we also studied the anti-tumor effect of GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms from the following aspects, including the performance test of the nanoplatform, the intracellular effect of the nanoplatform, the anti-tumor effect in vitro, the intracellular ROS analysis, the intracellular effect of EC, and the anti-tumor effect in vivo.</p><p><strong>Results: </strong>The iron-based carriers in GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms are released and produce ferrous ions (Fe<sup>2+</sup>) in an acidic environment. Due to the limitation of the endogenous level of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), we introduced GOx into the TME or tumor cells. Under the catalysis of GOx, glucose reacted rapidly to produce a large amount of H<sub>2</sub>O<sub>2</sub>, which then combined with Fe<sup>2+</sup> to produce a large number of Hydroxyl radical (·OH). Its toxicity leads to dysfunction of cell membrane and organelles, and then causes cell damage. EC inhibits Nuclear factor erythroid 2-related factor 2 (Nrf2) in cancer cells, which effectively down-regulates downstream gene products, including NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HMOX1). A series of chain reactions reduce the escape effect of oxidative stress (OS) and effectively maintain a high level of intracellular oxidation. Furthermore, it induces sustained and intense ferroptosis in tumor cells. Finally, the use of cancer cell membrane modified nanoplatforms due to the homology of membrane protein components improves the tumor cell targeting of the nanoplatforms, showing significant tumor cell inhibition and killing effect in vivo.</p><p><strong>Conclusion: </strong>The results showed that the GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms successfully induced significant ferroptosis of Hepatocellular carcinoma cells through a cascade effect, and finally effectively promoted cancer cel
{"title":"Iron-Based Nanoplatforms Achieve Hepatocellular Carcinoma Regression Through a Cascade of Effects.","authors":"Kunzhao Huang, Xiaoyuan Yi, Huaying Xie, Jianzhang Luo, Qingyu Zeng, Feifei He, Liyan Wang","doi":"10.2147/IJN.S479425","DOIUrl":"10.2147/IJN.S479425","url":null,"abstract":"<p><strong>Purpose: </strong>Ferroptosis is a regulated form of cell death characterized by iron-dependent accumulation of associated lipid peroxides (LPO), which can induce cell death when a certain level is reached. However, the extremely complex tumor microenvironment (TME) has the characteristics of antioxidant, even if it induces ferroptosis of tumor cells, its killing effect on tumor cells is still very limited. To solve this problem, we constructed a novel nanomaterials (GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM). We evaluated the anticancer effect of this nanomaterial in inhibiting tumor growth through comprehensive in vitro and in vivo experiments.</p><p><strong>Methods: </strong>We successfully synthesized GOx/EC@Fe<sub>3</sub>O<sub>4</sub> by one-pan synthesis method, then coated the Hepatocellular carcinoma cell membrane on its surface by co-extrusion technology, and finally synthesized the GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms. We characterized the compounds in terms of morphology, particle size, and Zeta potential. In addition, we also studied the anti-tumor effect of GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms from the following aspects, including the performance test of the nanoplatform, the intracellular effect of the nanoplatform, the anti-tumor effect in vitro, the intracellular ROS analysis, the intracellular effect of EC, and the anti-tumor effect in vivo.</p><p><strong>Results: </strong>The iron-based carriers in GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms are released and produce ferrous ions (Fe<sup>2+</sup>) in an acidic environment. Due to the limitation of the endogenous level of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), we introduced GOx into the TME or tumor cells. Under the catalysis of GOx, glucose reacted rapidly to produce a large amount of H<sub>2</sub>O<sub>2</sub>, which then combined with Fe<sup>2+</sup> to produce a large number of Hydroxyl radical (·OH). Its toxicity leads to dysfunction of cell membrane and organelles, and then causes cell damage. EC inhibits Nuclear factor erythroid 2-related factor 2 (Nrf2) in cancer cells, which effectively down-regulates downstream gene products, including NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HMOX1). A series of chain reactions reduce the escape effect of oxidative stress (OS) and effectively maintain a high level of intracellular oxidation. Furthermore, it induces sustained and intense ferroptosis in tumor cells. Finally, the use of cancer cell membrane modified nanoplatforms due to the homology of membrane protein components improves the tumor cell targeting of the nanoplatforms, showing significant tumor cell inhibition and killing effect in vivo.</p><p><strong>Conclusion: </strong>The results showed that the GOx/EC@Fe<sub>3</sub>O<sub>4</sub>@CCM nanoplatforms successfully induced significant ferroptosis of Hepatocellular carcinoma cells through a cascade effect, and finally effectively promoted cancer cel","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"19 ","pages":"11105-11128"},"PeriodicalIF":6.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}