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Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-04 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S500159
Aisha Khan, Julia Oliveira, Yee-Shuan Lee, James D Guest, Risset Silvera, Yelena Pressman, Damien D Pearse, Adriana E Nettina, Pascal J Goldschmidt-Clermont, Hassan Al-Ali, Indigo Williams, Allan D Levi, W Dalton Dietrich

Purpose: Schwann cell-derived extracellular vesicles (SCEVs) have demonstrated favorable effects in spinal cord, peripheral nerve, and brain injuries. Herein, a scalable, standardized, and efficient isolation methodology of SCEVs obtaining a high yield with a consistent composition as measured by proteomic, lipidomic, and miRNA analysis of their content is described for future clinical use.

Methods: Human Schwann cells were obtained ethically from nine donors and cultured in a defined growth medium optimized for proliferation. At confluency, the culture was replenished with an isolation medium for 48 hours, then collected and centrifuged sequentially at low and ultra-high speeds to collect purified EVs. The EVs were characterized with mass spectrometry to identify and quantify proteins, lipidomic analysis to assess lipid composition, and next-generation sequencing to confirm miRNA profiles. Each batch of EVs was assessed to ensure their therapeutic potential in promoting neurite outgrowth and cell survival.

Results: High yields of SCEVs were consistently obtained with similar comprehensive molecular profiles across samples, indicating the reproducibility and reliability of the isolation method. Bioactivity to increase neurite process growth was confirmed in vitro. The predominance of triacylglycerol and phosphatidylcholine suggested its role in cellular membrane dynamics essential for axon regeneration and inflammation mitigation. Of the 2517 identified proteins, 136 were closely related to nervous system repair and regeneration. A total of 732 miRNAs were cataloged, with the top 30 miRNAs potentially contributing to axon growth, neuroprotection, myelination, angiogenesis, the attenuation of neuroinflammation, and key signaling pathways such as VEGFA-VEGFR2 and PI3K-Akt signaling, which are crucial for nervous system repair.

Conclusion: The study establishes a robust framework for SCEV isolation and their comprehensive characterization, which is consistent with their therapeutic potential in neurological applications. This work provides a valuable proteomic, lipidomic, and miRNA dataset to inform future advancements in applying SCEV to the experimental treatment of neurological injuries and diseases.

{"title":"Human Schwann Cell-Derived Extracellular Vesicle Isolation, Bioactivity Assessment, and Omics Characterization.","authors":"Aisha Khan, Julia Oliveira, Yee-Shuan Lee, James D Guest, Risset Silvera, Yelena Pressman, Damien D Pearse, Adriana E Nettina, Pascal J Goldschmidt-Clermont, Hassan Al-Ali, Indigo Williams, Allan D Levi, W Dalton Dietrich","doi":"10.2147/IJN.S500159","DOIUrl":"https://doi.org/10.2147/IJN.S500159","url":null,"abstract":"<p><strong>Purpose: </strong>Schwann cell-derived extracellular vesicles (SCEVs) have demonstrated favorable effects in spinal cord, peripheral nerve, and brain injuries. Herein, a scalable, standardized, and efficient isolation methodology of SCEVs obtaining a high yield with a consistent composition as measured by proteomic, lipidomic, and miRNA analysis of their content is described for future clinical use.</p><p><strong>Methods: </strong>Human Schwann cells were obtained ethically from nine donors and cultured in a defined growth medium optimized for proliferation. At confluency, the culture was replenished with an isolation medium for 48 hours, then collected and centrifuged sequentially at low and ultra-high speeds to collect purified EVs. The EVs were characterized with mass spectrometry to identify and quantify proteins, lipidomic analysis to assess lipid composition, and next-generation sequencing to confirm miRNA profiles. Each batch of EVs was assessed to ensure their therapeutic potential in promoting neurite outgrowth and cell survival.</p><p><strong>Results: </strong>High yields of SCEVs were consistently obtained with similar comprehensive molecular profiles across samples, indicating the reproducibility and reliability of the isolation method. Bioactivity to increase neurite process growth was confirmed in vitro. The predominance of triacylglycerol and phosphatidylcholine suggested its role in cellular membrane dynamics essential for axon regeneration and inflammation mitigation. Of the 2517 identified proteins, 136 were closely related to nervous system repair and regeneration. A total of 732 miRNAs were cataloged, with the top 30 miRNAs potentially contributing to axon growth, neuroprotection, myelination, angiogenesis, the attenuation of neuroinflammation, and key signaling pathways such as VEGFA-VEGFR2 and PI3K-Akt signaling, which are crucial for nervous system repair.</p><p><strong>Conclusion: </strong>The study establishes a robust framework for SCEV isolation and their comprehensive characterization, which is consistent with their therapeutic potential in neurological applications. This work provides a valuable proteomic, lipidomic, and miRNA dataset to inform future advancements in applying SCEV to the experimental treatment of neurological injuries and diseases.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4123-4144"},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810489","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}
引用次数: 0
Internal-External Homologous Drug-Loaded Exosome-Like Nanovesicles Released from Semi-IPN Hydrogel Enhancing Wound Healing of Chemoradiotherapy-Induced Oral Mucositis.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-04 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S508530
Xiangjuan Wei, Mengyuan Wang, Xiaocong Dong, Yichen He, Wenbin Nan, Shenglu Ji, Mengyuan Zhao, Haodang Chang, Hongliang Wei, Dan Ding, Hongli Chen

Background: Oral mucositis (OM) is a common acute side effect among patients undergoing chemotherapy and/or radiotherapy, with complex pathogenesis and limited current treatment efficacy. Rabdosia rubescens, a traditional Chinese herb, contains oridonin (ORI) with antibacterial and anti - inflammatory properties. However, ORI's poor solubility and low bioavailability hamper its clinical use. Medicinal plant - derived exosome - like nanovesicles (ENs) are emerging as a promising drug delivery system for wound repair. This study aimed to develop a novel therapeutic approach.

Methods: We fabricated internally-externally homologous drug-loaded exosome-like nanovesicles (ORI/ENs) derived from Rabdosia rubescens and encapsulated them in a semi-interpenetrating network hydrogel system (ORI/ENs/Gel) to repair chemoradiotherapy-induced OM. The morphology, biocompatibility, and antibacterial properties were evaluated. Moreover, the proliferative and migratory capacity were measured using L929 cells. In addition, the pro-healing effects and the underlying molecular mechanisms of ORI/ENs/Gel were assessed in vivo.

Results: ENs were extracted and purified from Rabdosia rubescens by sequential ultra-centrifugations. The encapsulation efficiency (EE) and loading capacity (LC) of ORI in ORI/ENs were 76.4 ± 3.2% and 9.21 ± 0.45%, respectively, suggesting that ENs had a high loading efficiency for homologous drug ORI. The evaluation of toxicity and antibacterial effects has been proven that ORI/ENs has biocompatibility and antibacterial properties. In vivo, ORI/ENs/Gel promoted collagen deposition, targeted NLRP3 to reduce inflammation, and accelerated OM wound healing.

Conclusion: The hydrogel composite incorporating internally-externally homologous drug-loaded ENs offers the potential to provide targeted therapy, improve bioavailability, and promote efficient healing of the OM.

背景:口腔黏膜炎(OM)是化疗和/或放疗患者常见的急性副作用,发病机制复杂,目前的治疗效果有限。豨莶草(Rabdosia rubescens)是一种传统中草药,含有具有抗菌和抗炎特性的奥利多宁(ORI)。然而,ORI 溶解性差、生物利用率低,妨碍了其临床应用。药用植物衍生的外泌体纳米颗粒(ENS)正在成为一种用于伤口修复的前景广阔的药物输送系统。本研究旨在开发一种新的治疗方法:方法:我们制备了源自红豆杉的内外同源药物外泌体纳米颗粒(ORI/ENs),并将其封装在半互穿网络水凝胶系统(ORI/ENs/Gel)中,用于修复化放疗引起的OM。对其形态、生物相容性和抗菌特性进行了评估。此外,还使用 L929 细胞测量了其增殖和迁移能力。此外,还在体内评估了 ORI/ENs/Gel 的促愈合作用及其分子机制:结果:通过连续超速离心法,从红豆杉中提取并纯化了ENs。ORI/ENs中ORI的包封效率(EE)和负载能力(LC)分别为76.4±3.2%和9.21±0.45%,表明ENs对同源药物ORI具有较高的负载效率。毒性和抗菌效果评估证明,ORI/ENs 具有生物相容性和抗菌性。在体内,ORI/ENs/凝胶可促进胶原蛋白沉积,靶向 NLRP3 减少炎症,并加速 OM 伤口愈合:水凝胶复合体结合了内外同源的药物负载ENs,具有提供靶向治疗、提高生物利用度和促进OM有效愈合的潜力。
{"title":"Internal-External Homologous Drug-Loaded Exosome-Like Nanovesicles Released from Semi-IPN Hydrogel Enhancing Wound Healing of Chemoradiotherapy-Induced Oral Mucositis.","authors":"Xiangjuan Wei, Mengyuan Wang, Xiaocong Dong, Yichen He, Wenbin Nan, Shenglu Ji, Mengyuan Zhao, Haodang Chang, Hongliang Wei, Dan Ding, Hongli Chen","doi":"10.2147/IJN.S508530","DOIUrl":"https://doi.org/10.2147/IJN.S508530","url":null,"abstract":"<p><strong>Background: </strong>Oral mucositis (OM) is a common acute side effect among patients undergoing chemotherapy and/or radiotherapy, with complex pathogenesis and limited current treatment efficacy. <i>Rabdosia rubescens</i>, a traditional Chinese herb, contains oridonin (ORI) with antibacterial and anti - inflammatory properties. However, ORI's poor solubility and low bioavailability hamper its clinical use. Medicinal plant - derived exosome - like nanovesicles (ENs) are emerging as a promising drug delivery system for wound repair. This study aimed to develop a novel therapeutic approach.</p><p><strong>Methods: </strong>We fabricated internally-externally homologous drug-loaded exosome-like nanovesicles (ORI/ENs) derived from <i>Rabdosia rubescens</i> and encapsulated them in a semi-interpenetrating network hydrogel system (ORI/ENs/Gel) to repair chemoradiotherapy-induced OM. The morphology, biocompatibility, and antibacterial properties were evaluated. Moreover, the proliferative and migratory capacity were measured using L929 cells. In addition, the pro-healing effects and the underlying molecular mechanisms of ORI/ENs/Gel were assessed in vivo.</p><p><strong>Results: </strong>ENs were extracted and purified from <i>Rabdosia rubescens</i> by sequential ultra-centrifugations. The encapsulation efficiency (EE) and loading capacity (LC) of ORI in ORI/ENs were 76.4 ± 3.2% and 9.21 ± 0.45%, respectively, suggesting that ENs had a high loading efficiency for homologous drug ORI. The evaluation of toxicity and antibacterial effects has been proven that ORI/ENs has biocompatibility and antibacterial properties. In vivo, ORI/ENs/Gel promoted collagen deposition, targeted NLRP3 to reduce inflammation, and accelerated OM wound healing.</p><p><strong>Conclusion: </strong>The hydrogel composite incorporating internally-externally homologous drug-loaded ENs offers the potential to provide targeted therapy, improve bioavailability, and promote efficient healing of the OM.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4105-4121"},"PeriodicalIF":6.6,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11977572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810696","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}
引用次数: 0
LIFU (Low-Intensity Focused Ultrasound) Activated Tumor-Starvation/Oxidative-Stress Combined Therapy for Treating Retinoblastoma.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-03 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S506179
Luya Quan, Mengzhu Wang, Zhigang Wang, Zhiyu Du

Purpose: To overcome the limitations of traditional therapies in treating retinoblastoma, like low efficiency, systematic toxicity and poor biocompatibility.

Materials and methods: PPFG (PLGA-PFH-Fe3O4-GOx) nanoparticles were synthesized by ultrasound double emulsification method and characterized by dynamic laser scattering, ultraviolet spectrometry, confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Phase transition by low-intensity focused ultrasound (LIFU) was observed by microscope and ultrasound imaging. Cellular uptake was compared between Y79 and HUVEC cells. ROS production was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA). Cell apoptosis was detected by flow cytometry. In vivo therapeutic effects were verified by tumor volume, HE staining, TUNEL and PCNA staining. The in vivo bio-safety was detected by serum biochemistry.

Results: PPFG NPs possesses good stability, biocompatibility and tumor-preferred uptake, with a core-shell spherical structure and an average size of 255.6nm which increases to over 100μm under LIFU irradiation. LIFU was utilized as a stimuli, by which PPFG NPs undergoes a sequential reaction starting with phase transition of PFH causing the release of the oxygen carried by PFH and GOx/SPIO carried by PPFG NPs, followed by the supplemented oxygen facilitating the enzymatic activity of glucose consumption by GOx in tumor cells (tumor starvation), the H2O2 produced during the enzymatic activity can further participate in SPIO NPs-mediated Fenton reaction (CDT), generating massive ROS. The continuously generated ROS together with the cut down of tumor nutrients by GOx effectively inhibited the progression of tumors, and synergistically enhanced ROS production together with tumor starvation promoted cell apoptosis and ultimately kills the tumour cells. No off-site injuries was detected in other major organs.

Conclusion: In this study, PPFG nanoparticles were synthesized to conduct LIFU-triggered combinational therapy on the basis of the cascade reaction among PFH, GOx and SPIO to treat retinoblastoma in vitro/vivo. It showed great potentials in combating retinoblastoma.

{"title":"LIFU (Low-Intensity Focused Ultrasound) Activated Tumor-Starvation/Oxidative-Stress Combined Therapy for Treating Retinoblastoma.","authors":"Luya Quan, Mengzhu Wang, Zhigang Wang, Zhiyu Du","doi":"10.2147/IJN.S506179","DOIUrl":"10.2147/IJN.S506179","url":null,"abstract":"<p><strong>Purpose: </strong>To overcome the limitations of traditional therapies in treating retinoblastoma, like low efficiency, systematic toxicity and poor biocompatibility.</p><p><strong>Materials and methods: </strong>PPFG (PLGA-PFH-Fe<sub>3</sub>O<sub>4</sub>-GOx) nanoparticles were synthesized by ultrasound double emulsification method and characterized by dynamic laser scattering, ultraviolet spectrometry, confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Phase transition by low-intensity focused ultrasound (LIFU) was observed by microscope and ultrasound imaging. Cellular uptake was compared between Y79 and HUVEC cells. ROS production was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA). Cell apoptosis was detected by flow cytometry. In vivo therapeutic effects were verified by tumor volume, HE staining, TUNEL and PCNA staining. The in vivo bio-safety was detected by serum biochemistry.</p><p><strong>Results: </strong>PPFG NPs possesses good stability, biocompatibility and tumor-preferred uptake, with a core-shell spherical structure and an average size of 255.6nm which increases to over 100μm under LIFU irradiation. LIFU was utilized as a stimuli, by which PPFG NPs undergoes a sequential reaction starting with phase transition of PFH causing the release of the oxygen carried by PFH and GOx/SPIO carried by PPFG NPs, followed by the supplemented oxygen facilitating the enzymatic activity of glucose consumption by GOx in tumor cells (tumor starvation), the H<sub>2</sub>O<sub>2</sub> produced during the enzymatic activity can further participate in SPIO NPs-mediated Fenton reaction (CDT), generating massive ROS. The continuously generated ROS together with the cut down of tumor nutrients by GOx effectively inhibited the progression of tumors, and synergistically enhanced ROS production together with tumor starvation promoted cell apoptosis and ultimately kills the tumour cells. No off-site injuries was detected in other major organs.</p><p><strong>Conclusion: </strong>In this study, PPFG nanoparticles were synthesized to conduct LIFU-triggered combinational therapy on the basis of the cascade reaction among PFH, GOx and SPIO to treat retinoblastoma in vitro/vivo. It showed great potentials in combating retinoblastoma.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4085-4103"},"PeriodicalIF":6.6,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803153","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}
引用次数: 0
Reactive Oxygen Species-Responsive Pyroptosis Nanoinitiators Promote Immune Cell Infiltration and Activate Anti-Tumor Immune Response.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-02 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S503580
Hongbo Yan, Yilun Liu, Maoshan Wang, Zhenbo Shu, Xuedong Fang, Zhongmin Li

Background: Immunotherapy, particularly immune checkpoint inhibitors, has become the standard treatment strategy for diverse malignant tumors. However, the inadequate infiltration of immune cells in tumors coupled with the immunosuppressive tumor microenvironment severely hinders the efficacy of immunotherapy.

Methods: A poly(ethylene glycol)-block-poly(lysine) copolymer (mPEG-b-PLL) was prepared through ring-opening polymerization and deprotection, and thioketal (TK) was attached to the amino group of mPEG-b-PLL via the condensation reaction to obtain mPEG-b-PLL-TK. Doxorubicin (DOX) and decitabine (DAC) were encapsulated in mPEG-b-PLL-TK to prepare the pyroptosis nanoinitiator (NP/(DAC+DOX)). The drug release behavior, cellular uptake, pyroptosis-triggering performance, and cytotoxicity of NP/(DAC+DOX) were evaluated in vitro experiments. The in vivo pharmacokinetics and biodistribution of NP/(DAC+DOX) were assessed through fluorescence imaging and high-performance liquid chromatography analysis. CT26 and 4T1 tumor-bearing mouse models were established to evaluate the anti-tumor efficacy, pyroptosis-triggering performance, and immune activation effects of NP/(DAC+DOX).

Results: NP/(DAC+DOX) exhibited excellent reactive oxygen species (ROS)-responsive drug release behavior and could be effectively taken up by tumor cells. Experiments both in vitro and in vivo demonstrated that NP/(DAC+DOX) effectively triggered pyroptosis in tumor cells, which was attributed to the DOX-induced activation of caspase-3 and the upregulation of GSDME expression caused by DAC. Following intravenous administration, NP/(DAC+DOX) specifically aggregated in tumor tissues. NP/(DAC+DOX) significantly suppressed tumor growth and extended the survival time of tumor-bearing mice. Furthermore, NP/(DAC+DOX) promoted dendritic cell maturation, enhanced the infiltration of cytotoxic T lymphocytes within the tumor, and decreased the proportion of myeloid-derived suppressor cells.

Conclusion: This study developed a ROS-responsive pyroptosis nanoinitiator to precisely induce the pyroptosis of tumor cells, thereby enhancing intratumoral immune cell infiltration and activating anti-tumor immune responses.

{"title":"Reactive Oxygen Species-Responsive Pyroptosis Nanoinitiators Promote Immune Cell Infiltration and Activate Anti-Tumor Immune Response.","authors":"Hongbo Yan, Yilun Liu, Maoshan Wang, Zhenbo Shu, Xuedong Fang, Zhongmin Li","doi":"10.2147/IJN.S503580","DOIUrl":"10.2147/IJN.S503580","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy, particularly immune checkpoint inhibitors, has become the standard treatment strategy for diverse malignant tumors. However, the inadequate infiltration of immune cells in tumors coupled with the immunosuppressive tumor microenvironment severely hinders the efficacy of immunotherapy.</p><p><strong>Methods: </strong>A poly(ethylene glycol)-<i>block</i>-poly(lysine) copolymer (mPEG-<i>b</i>-PLL) was prepared through ring-opening polymerization and deprotection, and thioketal (TK) was attached to the amino group of mPEG-<i>b</i>-PLL via the condensation reaction to obtain mPEG-<i>b</i>-PLL-TK. Doxorubicin (DOX) and decitabine (DAC) were encapsulated in mPEG-<i>b</i>-PLL-TK to prepare the pyroptosis nanoinitiator (NP/(DAC+DOX)). The drug release behavior, cellular uptake, pyroptosis-triggering performance, and cytotoxicity of NP/(DAC+DOX) were evaluated in vitro experiments. The in vivo pharmacokinetics and biodistribution of NP/(DAC+DOX) were assessed through fluorescence imaging and high-performance liquid chromatography analysis. CT26 and 4T1 tumor-bearing mouse models were established to evaluate the anti-tumor efficacy, pyroptosis-triggering performance, and immune activation effects of NP/(DAC+DOX).</p><p><strong>Results: </strong>NP/(DAC+DOX) exhibited excellent reactive oxygen species (ROS)-responsive drug release behavior and could be effectively taken up by tumor cells. Experiments both in vitro and in vivo demonstrated that NP/(DAC+DOX) effectively triggered pyroptosis in tumor cells, which was attributed to the DOX-induced activation of caspase-3 and the upregulation of GSDME expression caused by DAC. Following intravenous administration, NP/(DAC+DOX) specifically aggregated in tumor tissues. NP/(DAC+DOX) significantly suppressed tumor growth and extended the survival time of tumor-bearing mice. Furthermore, NP/(DAC+DOX) promoted dendritic cell maturation, enhanced the infiltration of cytotoxic T lymphocytes within the tumor, and decreased the proportion of myeloid-derived suppressor cells.</p><p><strong>Conclusion: </strong>This study developed a ROS-responsive pyroptosis nanoinitiator to precisely induce the pyroptosis of tumor cells, thereby enhancing intratumoral immune cell infiltration and activating anti-tumor immune responses.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4069-4084"},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795343","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}
引用次数: 0
Mechanism of a Novel Complex: Zinc Oxide Nanoparticles-Luteolin to Promote Ferroptosis in Human Acute Myeloid Leukemia Cells in Vitro.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-02 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S509007
Wenhao Wang, Zonghong Li, Chunyi Lyu, Teng Wang, Chen Han, Siyuan Cui, Jinxin Wang, Ruirong Xu

Purpose: Acute myeloid leukemia (AML) is a hematological malignancy. Zinc oxide nanoparticles (ZnO NPs) and Luteolin are commonly used to fight cancer. In this study, we synthesized a new complex: zinc oxide nanoparticles-luteolin (ZnONPs-Lut) and aimed to investigate its effects on cell death in the AML cell line (MOLM-13) in vitro and to elucidate the underlying mechanisms.

Methods: We assessed cell viability, quantified changes in gene expression using real-time quantitative PCR (qRT-PCR), and measured changes in ferrous (Fe2+) content, glutathione (GSH) content, malondialdehyde (MDA) content, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) levels following treatment with different concentrations of MOLM-13 cells with different concentrations of ZnONPs-Lut. Western blotting was used to detect the protein expression levels of ACSL4, GPX4, FTH1, and SLC7A11, while the cell morphology was observed by transmission electron microscopy (TEM). Meanwhile, the effect of Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, on the expression of the aforementioned ferroptosis-related proteins and cell morphology was evaluated.

Results: The results showed that ZnONPs-Lut was able to significantly inhibit the proliferation of MOLM-13 cells in a time- and dose-dependent manner. Additionally, it increased the concentrations of Fe2+ and MDA, reduced the expression levels of GSH and MMP, and induced ROS generation. Furthermore, it also enhanced the expression of ACSL4 protein while decreasing the expression of GPX4, FTH1, and SLC7A11 proteins. Notably, Fer-1 was able to significantly restrain the changes in protein levels and mitochondrial morphology damage induced by ZnONPs-Lut after its action on cells.

Conclusion: ZnONPs-Lut inhibits the proliferation of MOLM-13 cells, likely through promoting the cellular ferroptosis signaling pathway. These findings suggest that ZnONPs-Lut could be a potential therapeutic approach for AML.

{"title":"Mechanism of a Novel Complex: Zinc Oxide Nanoparticles-Luteolin to Promote Ferroptosis in Human Acute Myeloid Leukemia Cells in Vitro.","authors":"Wenhao Wang, Zonghong Li, Chunyi Lyu, Teng Wang, Chen Han, Siyuan Cui, Jinxin Wang, Ruirong Xu","doi":"10.2147/IJN.S509007","DOIUrl":"10.2147/IJN.S509007","url":null,"abstract":"<p><strong>Purpose: </strong>Acute myeloid leukemia (AML) is a hematological malignancy. Zinc oxide nanoparticles (ZnO NPs) and Luteolin are commonly used to fight cancer. In this study, we synthesized a new complex: zinc oxide nanoparticles-luteolin (ZnONPs-Lut) and aimed to investigate its effects on cell death in the AML cell line (MOLM-13) in vitro and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>We assessed cell viability, quantified changes in gene expression using real-time quantitative PCR (qRT-PCR), and measured changes in ferrous (Fe<sup>2+</sup>) content, glutathione (GSH) content, malondialdehyde (MDA) content, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) levels following treatment with different concentrations of MOLM-13 cells with different concentrations of ZnONPs-Lut. Western blotting was used to detect the protein expression levels of ACSL4, GPX4, FTH1, and SLC7A11, while the cell morphology was observed by transmission electron microscopy (TEM). Meanwhile, the effect of Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, on the expression of the aforementioned ferroptosis-related proteins and cell morphology was evaluated.</p><p><strong>Results: </strong>The results showed that ZnONPs-Lut was able to significantly inhibit the proliferation of MOLM-13 cells in a time- and dose-dependent manner. Additionally, it increased the concentrations of Fe<sup>2+</sup> and MDA, reduced the expression levels of GSH and MMP, and induced ROS generation. Furthermore, it also enhanced the expression of ACSL4 protein while decreasing the expression of GPX4, FTH1, and SLC7A11 proteins. Notably, Fer-1 was able to significantly restrain the changes in protein levels and mitochondrial morphology damage induced by ZnONPs-Lut after its action on cells.</p><p><strong>Conclusion: </strong>ZnONPs-Lut inhibits the proliferation of MOLM-13 cells, likely through promoting the cellular ferroptosis signaling pathway. These findings suggest that ZnONPs-Lut could be a potential therapeutic approach for AML.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4035-4050"},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795322","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}
引用次数: 0
Aloe Vera Gel and Rind-Derived Nanoparticles Mitigate Skin Photoaging via Activation of Nrf2/ARE Pathway.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-02 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S510352
Zixuan Sun, Yuzhou Zheng, Tangrong Wang, Jiaxin Zhang, Jiali Li, Zhijing Wu, Fan Zhang, Tingxin Gao, Li Yu, XueZhong Xu, Hui Qian, Yulin Tan

Background: Skin aging is the primary external manifestation of human aging, and long-term exposure to ultraviolet radiation is the leading cause of photoaging, which can lead to actinic keratosis and skin cancer in severe cases. Traditional treatments may pose safety risks and cause side effects. As an emerging research direction, plant-derived exosome-like nanoparticles (PDNPs) show promise in combating aging. Aloe vera, known for its natural active ingredients that benefit the skin, aloe-derived exosome-like nanoparticles (ADNPs) have not yet been studied for their potential in delaying skin aging.

Methods: In this study, nanoparticles were isolated from two different sites, aloe vera gel and aloe vera rind (gADNPs and rADNPs), and characterized by TEM, SEM, AFM, NTA and BCA. The effects were evaluated by constructing in vitro and in vivo models and using RT-qPCR, immunofluorescence, and histopathological analysis.

Results: The results first revealed the exceptional anti-aging effects of ADNPs. We found that ADNPs promoted the nuclear translocation of Nrf2, alleviated oxidative stress and DNA damage induced by UV exposure, and inhibited the elevation of β-gal and SASP. In vivo, ADNPs reduced MDA and SOD levels in mouse skin tissue and delayed skin photoaging. Moreover, safety assessments confirmed the excellent biocompatibility of ADNPs.

Conclusion: ADNPs delay skin photoaging through the Nrf2/ARE pathway, holding potential clinical application value, and may provide new therapeutic strategies for future medical cosmetology and skin disease prevention.

{"title":"<i>Aloe Vera</i> Gel and Rind-Derived Nanoparticles Mitigate Skin Photoaging via Activation of Nrf2/ARE Pathway.","authors":"Zixuan Sun, Yuzhou Zheng, Tangrong Wang, Jiaxin Zhang, Jiali Li, Zhijing Wu, Fan Zhang, Tingxin Gao, Li Yu, XueZhong Xu, Hui Qian, Yulin Tan","doi":"10.2147/IJN.S510352","DOIUrl":"10.2147/IJN.S510352","url":null,"abstract":"<p><strong>Background: </strong>Skin aging is the primary external manifestation of human aging, and long-term exposure to ultraviolet radiation is the leading cause of photoaging, which can lead to actinic keratosis and skin cancer in severe cases. Traditional treatments may pose safety risks and cause side effects. As an emerging research direction, plant-derived exosome-like nanoparticles (PDNPs) show promise in combating aging. <i>Aloe vera</i>, known for its natural active ingredients that benefit the skin, aloe-derived exosome-like nanoparticles (ADNPs) have not yet been studied for their potential in delaying skin aging.</p><p><strong>Methods: </strong>In this study, nanoparticles were isolated from two different sites, <i>aloe vera</i> gel and <i>aloe vera</i> rind (gADNPs and rADNPs), and characterized by TEM, SEM, AFM, NTA and BCA. The effects were evaluated by constructing in vitro and in vivo models and using RT-qPCR, immunofluorescence, and histopathological analysis.</p><p><strong>Results: </strong>The results first revealed the exceptional anti-aging effects of ADNPs. We found that ADNPs promoted the nuclear translocation of Nrf2, alleviated oxidative stress and DNA damage induced by UV exposure, and inhibited the elevation of β-gal and SASP. In vivo, ADNPs reduced MDA and SOD levels in mouse skin tissue and delayed skin photoaging. Moreover, safety assessments confirmed the excellent biocompatibility of ADNPs.</p><p><strong>Conclusion: </strong>ADNPs delay skin photoaging through the Nrf2/ARE pathway, holding potential clinical application value, and may provide new therapeutic strategies for future medical cosmetology and skin disease prevention.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4051-4067"},"PeriodicalIF":6.6,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795356","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}
引用次数: 0
Adjuvanticity of Tannic Acid-Modified Nanoparticles Improves Effectiveness of the Antiviral Response.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S512509
Martyna Janicka, Marcin Chodkowski, Aleksandra Osinska, Klaudia Bylinska, Oliwia Obuch-Woszczatyńska, Magdalena Patrycy, Grzegorz Chodaczek, Katarzyna Ranoszek-Soliwoda, Emilia Tomaszewska, Grzegorz Celichowski, Jaroslaw Grobelny, Joanna Cymerys, Małgorzata Krzyżowska

Introduction: Herpes simplex virus type 1 (HSV-1) causes recurrent infections of skin and mucosal tissues with high global prevalence. HSV-1 also invades the nervous system where it establishes a lifelong latency-making infection poorly treatable We previously showed that both tannic acid-modified silver and gold nanoparticles (TA-Ag/AuNPs) inhibit HSV-1 infection in vitro.

Methods: We used an in vitro and in vivo model of HSV-1 infection to study how metal type, size and tannic acid modification of nanoparticles can influence development of the early innate response and the mounting of specific anti-HSV-1 response upon treatment of the nasal mucosa.

Results: We found that tannic acid is necessary for binding with HSV-1, with smaller sizes independent of the NPs composition, whereas for larger NPs, only TA-AgNPs can inhibit HSV-1 infection. Intranasal treatment of HSV-1 infection with TA-Ag/AuNPs results in lower viral titers and a better antiviral response, followed by increased IFN-α, CXCL9, and CXCL10 levels as well as infiltration of T cells and NK cells in the infected sites. We also found that the application of TA-NPs to the nasal cavities of infected mice induced infiltration of both monocytes and Langerhans cells (LCs), which lasted longer compared to the application of unmodified NPs. Furthermore, TA-NPs activated monocytes and microglia to produce antiviral cytokines and chemokines better than unmodified NPs, except for the large TA-AuNPs.

Discussion: Treatment of the mucosal tissues at the early stage of HSV-1 infection helps to modulate specific and effective antiviral immune response by attracting cytotoxic lymphocytes and inducing the production of antiviral cytokines and chemokines. Furthermore, tannic acid modification is helpful for the removal of nanoparticles from the respiratory tract, which increases the safety of nanoparticle applications to treat infections.

{"title":"Adjuvanticity of Tannic Acid-Modified Nanoparticles Improves Effectiveness of the Antiviral Response.","authors":"Martyna Janicka, Marcin Chodkowski, Aleksandra Osinska, Klaudia Bylinska, Oliwia Obuch-Woszczatyńska, Magdalena Patrycy, Grzegorz Chodaczek, Katarzyna Ranoszek-Soliwoda, Emilia Tomaszewska, Grzegorz Celichowski, Jaroslaw Grobelny, Joanna Cymerys, Małgorzata Krzyżowska","doi":"10.2147/IJN.S512509","DOIUrl":"10.2147/IJN.S512509","url":null,"abstract":"<p><strong>Introduction: </strong>Herpes simplex virus type 1 (HSV-1) causes recurrent infections of skin and mucosal tissues with high global prevalence. HSV-1 also invades the nervous system where it establishes a lifelong latency-making infection poorly treatable We previously showed that both tannic acid-modified silver and gold nanoparticles (TA-Ag/AuNPs) inhibit HSV-1 infection in vitro.</p><p><strong>Methods: </strong>We used an in vitro and in vivo model of HSV-1 infection to study how metal type, size and tannic acid modification of nanoparticles can influence development of the early innate response and the mounting of specific anti-HSV-1 response upon treatment of the nasal mucosa.</p><p><strong>Results: </strong>We found that tannic acid is necessary for binding with HSV-1, with smaller sizes independent of the NPs composition, whereas for larger NPs, only TA-AgNPs can inhibit HSV-1 infection. Intranasal treatment of HSV-1 infection with TA-Ag/AuNPs results in lower viral titers and a better antiviral response, followed by increased IFN-α, CXCL9, and CXCL10 levels as well as infiltration of T cells and NK cells in the infected sites. We also found that the application of TA-NPs to the nasal cavities of infected mice induced infiltration of both monocytes and Langerhans cells (LCs), which lasted longer compared to the application of unmodified NPs. Furthermore, TA-NPs activated monocytes and microglia to produce antiviral cytokines and chemokines better than unmodified NPs, except for the large TA-AuNPs.</p><p><strong>Discussion: </strong>Treatment of the mucosal tissues at the early stage of HSV-1 infection helps to modulate specific and effective antiviral immune response by attracting cytotoxic lymphocytes and inducing the production of antiviral cytokines and chemokines. Furthermore, tannic acid modification is helpful for the removal of nanoparticles from the respiratory tract, which increases the safety of nanoparticle applications to treat infections.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3977-3997"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795306","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}
引用次数: 0
Polyethylenimine-Conjugated Au-NPs as an Efficient Vehicle for in vitro and in vivo DNA Vaccine Delivery.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S493211
Aras Kartouzian, Alexandra Heiz, Kamyar Shameli, Hassan Moeini

Purpose: This study aimed to develop green-synthesized gold nanoparticles (Au-NPs) conjugated with polyethyleneimine (PEI) to overcome challenges in intracellular DNA vaccine delivery, focusing on enhancing cellular uptake and immune responses against the human norovirus (HuNoV) GII.4 variants.

Methods: Au-NPs were synthesized using a citrate-ion-mediated green approach, with size and morphology analyzed via UV-vis spectroscopy and transmission electron microscopy (TEM). Stability was evaluated through zeta potential measurements. PEI conjugation was employed to modify surface charge. After in vitro evaluation of pDNA delivery efficiency and cytotoxicity in HEK293 cells, PEI-coated Au-NPs loaded with a HuNoV GII.4 pDNA vaccine (AuPEI-NPs-pDNA) were assessed for the immune responses in mice.

Results: UV-vis spectroscopy and TEM confirmed successful Au-NP synthesis. Zeta potential shifted from -31.38 mV to -20.60 mV, reflecting stable but slightly reduced colloidal stability with larger sizes. PEI conjugation reversed surface charge to positive, enabling 100% transfection efficacy in HEK293 cells by day two without cytotoxicity. The AuPEI-NPs-pDNA induced significantly higher NoV-specific IgG antibodies and T-cell responses compared to unmodified Au-NPs, highlighting the role of positive charge in enhancing cellular uptake and immune activation. These results underscore PEI-coated Au-NPs as a biocompatible, efficient platform for DNA vaccine delivery.

Conclusion: PEI-coated Au-NPs demonstrate exceptional potential as non-toxic, high-efficiency carriers for DNA vaccines, enabling robust humoral and cellular immune responses. This strategy holds promises for advancing gene therapy and combating rapidly evolving pathogens like HuNoV, with broader applications in targeted drug delivery.

{"title":"Polyethylenimine-Conjugated Au-NPs as an Efficient Vehicle for in vitro and in vivo DNA Vaccine Delivery.","authors":"Aras Kartouzian, Alexandra Heiz, Kamyar Shameli, Hassan Moeini","doi":"10.2147/IJN.S493211","DOIUrl":"10.2147/IJN.S493211","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop green-synthesized gold nanoparticles (Au-NPs) conjugated with polyethyleneimine (PEI) to overcome challenges in intracellular DNA vaccine delivery, focusing on enhancing cellular uptake and immune responses against the human norovirus (HuNoV) GII.4 variants.</p><p><strong>Methods: </strong>Au-NPs were synthesized using a citrate-ion-mediated green approach, with size and morphology analyzed via UV-vis spectroscopy and transmission electron microscopy (TEM). Stability was evaluated through zeta potential measurements. PEI conjugation was employed to modify surface charge. After in vitro evaluation of pDNA delivery efficiency and cytotoxicity in HEK293 cells, PEI-coated Au-NPs loaded with a HuNoV GII.4 pDNA vaccine (AuPEI-NPs-pDNA) were assessed for the immune responses in mice.</p><p><strong>Results: </strong>UV-vis spectroscopy and TEM confirmed successful Au-NP synthesis. Zeta potential shifted from -31.38 mV to -20.60 mV, reflecting stable but slightly reduced colloidal stability with larger sizes. PEI conjugation reversed surface charge to positive, enabling 100% transfection efficacy in HEK293 cells by day two without cytotoxicity. The AuPEI-NPs-pDNA induced significantly higher NoV-specific IgG antibodies and T-cell responses compared to unmodified Au-NPs, highlighting the role of positive charge in enhancing cellular uptake and immune activation. These results underscore PEI-coated Au-NPs as a biocompatible, efficient platform for DNA vaccine delivery.</p><p><strong>Conclusion: </strong>PEI-coated Au-NPs demonstrate exceptional potential as non-toxic, high-efficiency carriers for DNA vaccines, enabling robust humoral and cellular immune responses. This strategy holds promises for advancing gene therapy and combating rapidly evolving pathogens like HuNoV, with broader applications in targeted drug delivery.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"4021-4034"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795325","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}
引用次数: 0
Preparation and Characterization of Mitochondrial-Targeted Nitronyl Nitroxide Loaded PLGA Nanoparticles for Brain Injury Induced by Hypobaric Hypoxia in Mice.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S507315
Qingyue Da, Min Xu, Yiting Tian, Huiping Ma, Haibo Wang, Linlin Jing

Background: Oxidative stress is considered an important mechanism of acute high-altitude brain injury. Imidazole nitronyl nitroxide radicals are a class of stable organic radical scavengers that contain single electrons in their molecules. Therefore, in order to search for compounds with low toxicity and better effect against high-altitude brain injury, the preparation methods of PLGA nanoparticles (TPP-C6-HPN@PLGA-NPs) loaded with a synthesized mitochondria targeting imidazole nitronyl nitroxide were emphasized and investigated. Furthermore, its protective effect on brain injury caused by low-pressure hypoxia (HH) in mice was evaluated.

Methods: Nanoparticles were prepared by emulsion solvent evaporation method, and the preparation method was optimized by Box Behnken design based on particle size, encapsulation efficiency (EE) and drug loading (DL). Physical characterization and release studies of the optimized NPs were conducted. The high altitude brain injury mice model was selected to evaluate the therapeutic effect of TPP-C6-HPN@PLGA-NPs in vivo. The histological and biochemical tests were conducted in serum and brain of mice exposed to HH condition.

Results: The nanoparticle size was 120.63 nm, the EE was 89.30%, the DL was 6.82%, the polydispersity index (PDI) was 0.172, and the zeta potential was -22.67 mV under optimal preparation process. In addition, TPP-C6-HPN@PLGA-NPs owned good stabilities and sustained drug releases. TPP-C6-HPN@PLGA-NP exhibited lower toxicity than TPP-C6-HPN and was well uptaken by PC12 cells. Histological and biochemical analysis demonstrated that TPP-C6-HPN@PLGA-NPs significantly reduced HH induced pathological lesions, oxidative stress, energy dysfunction and inflammation response of brain tissue. Furthermore, nanoparticles did not show significant toxicity to major organs such as the liver and kidneys, as well as hematology in mice.

Conclusion: TPP-C6-HPN@PLGA-NPs exhibits good stability, low hemolysis rate, sustained release, low toxicity, and long residence time in brain tissue and can be used as a promising formulation for the proper treatment of HH-induced brain damage.

背景:氧化应激被认为是急性高海拔脑损伤的一个重要机制。咪唑亚硝基是一类稳定的有机自由基清除剂,其分子中含有单个电子。因此,为了寻找低毒且对高海拔脑损伤有较好疗效的化合物,重点研究了以合成的线粒体靶向亚硝基咪唑为载体的 PLGA 纳米颗粒(TPP-C6-HPN@PLGA-NPs)的制备方法。此外,还评估了其对低压缺氧(HH)引起的小鼠脑损伤的保护作用:方法:采用乳液溶剂蒸发法制备纳米颗粒,并根据粒径、包封效率(EE)和载药量(DL)对制备方法进行盒式贝肯设计(Box Behnken design)优化。对优化后的 NPs 进行了物理表征和释放研究。选择高海拔脑损伤小鼠模型来评估 TPP-C6-HPN@PLGA-NPs 在体内的治疗效果。对暴露于高海拔条件下的小鼠血清和大脑进行了组织学和生化测试:结果:在最佳制备工艺下,TPP-C6-HPN@PLGA-NPs的粒径为120.63 nm,EE为89.30%,DL为6.82%,多分散指数(PDI)为0.172,zeta电位为-22.67 mV。此外,TPP-C6-HPN@PLGA-NPs 还具有良好的稳定性和药物持续释放性。与 TPP-C6-HPN 相比,TPP-C6-HPN@PLGA-NP 的毒性更低,且能被 PC12 细胞很好地吸收。组织学和生化分析表明,TPP-C6-HPN@PLGA-NPs 能显著减少 HH 诱导的脑组织病变、氧化应激、能量功能障碍和炎症反应。此外,纳米颗粒对小鼠的肝脏、肾脏等主要器官以及血液学没有明显毒性:结论:TPP-C6-HPN@PLGA-NPs 具有稳定性好、溶血率低、持续释放、毒性低和在脑组织中停留时间长等特点,可作为一种有前途的制剂用于适当治疗 HH 引起的脑损伤。
{"title":"Preparation and Characterization of Mitochondrial-Targeted Nitronyl Nitroxide Loaded PLGA Nanoparticles for Brain Injury Induced by Hypobaric Hypoxia in Mice.","authors":"Qingyue Da, Min Xu, Yiting Tian, Huiping Ma, Haibo Wang, Linlin Jing","doi":"10.2147/IJN.S507315","DOIUrl":"10.2147/IJN.S507315","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress is considered an important mechanism of acute high-altitude brain injury. Imidazole nitronyl nitroxide radicals are a class of stable organic radical scavengers that contain single electrons in their molecules. Therefore, in order to search for compounds with low toxicity and better effect against high-altitude brain injury, the preparation methods of PLGA nanoparticles (TPP-C<sub>6</sub>-HPN@PLGA-NPs) loaded with a synthesized mitochondria targeting imidazole nitronyl nitroxide were emphasized and investigated. Furthermore, its protective effect on brain injury caused by low-pressure hypoxia (HH) in mice was evaluated.</p><p><strong>Methods: </strong>Nanoparticles were prepared by emulsion solvent evaporation method, and the preparation method was optimized by Box Behnken design based on particle size, encapsulation efficiency (EE) and drug loading (DL). Physical characterization and release studies of the optimized NPs were conducted. The high altitude brain injury mice model was selected to evaluate the therapeutic effect of TPP-C<sub>6</sub>-HPN@PLGA-NPs in vivo. The histological and biochemical tests were conducted in serum and brain of mice exposed to HH condition.</p><p><strong>Results: </strong>The nanoparticle size was 120.63 nm, the EE was 89.30%, the DL was 6.82%, the polydispersity index (PDI) was 0.172, and the zeta potential was -22.67 mV under optimal preparation process. In addition, TPP-C<sub>6</sub>-HPN@PLGA-NPs owned good stabilities and sustained drug releases. TPP-C<sub>6</sub>-HPN@PLGA-NP exhibited lower toxicity than TPP-C<sub>6</sub>-HPN and was well uptaken by PC12 cells. Histological and biochemical analysis demonstrated that TPP-C<sub>6</sub>-HPN@PLGA-NPs significantly reduced HH induced pathological lesions, oxidative stress, energy dysfunction and inflammation response of brain tissue. Furthermore, nanoparticles did not show significant toxicity to major organs such as the liver and kidneys, as well as hematology in mice.</p><p><strong>Conclusion: </strong>TPP-C<sub>6</sub>-HPN@PLGA-NPs exhibits good stability, low hemolysis rate, sustained release, low toxicity, and long residence time in brain tissue and can be used as a promising formulation for the proper treatment of HH-induced brain damage.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3999-4020"},"PeriodicalIF":6.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795328","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}
引用次数: 0
Recent Research Progress of Wound Healing Biomaterials Containing Platelet-Rich Plasma.
IF 6.6 2区 医学 Q1 NANOSCIENCE & NANOTECHNOLOGY Pub Date : 2025-03-31 eCollection Date: 2025-01-01 DOI: 10.2147/IJN.S506677
Sha Huang, Qing Li, Xiangyu Li, Hailing Ye, Luyang Zhang, Xiaoyi Zhu

Platelet-Rich Plasma (PRP) is a plasma product obtained by centrifuging autologous blood, containing a high concentration of platelets, white blood cells, and fibrin. PRP is enriched with various growth factors, such as Transforming Growth Factor-beta (TGF-β), Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF), Insulin-Like Growth Factor (IGF), and Vascular Endothelial Growth Factor (VEGF), all of which promote tissue growth and repair. Currently, PRP has been widely applied in the clinical field of wound repair and has achieved certain therapeutic effects. Biomaterials, as an important direction in the treatment of wounds, combined with PRP, provide new possibilities to enhance the regenerative repair of wounds by PRP. This article reviews the latest research progress of biomaterials combined with PRP in the treatment of wounds, aiming to provide references for PRP wound treatment, as well as to provide ideas for the development of subsequent medical materials.

{"title":"Recent Research Progress of Wound Healing Biomaterials Containing Platelet-Rich Plasma.","authors":"Sha Huang, Qing Li, Xiangyu Li, Hailing Ye, Luyang Zhang, Xiaoyi Zhu","doi":"10.2147/IJN.S506677","DOIUrl":"10.2147/IJN.S506677","url":null,"abstract":"<p><p>Platelet-Rich Plasma (PRP) is a plasma product obtained by centrifuging autologous blood, containing a high concentration of platelets, white blood cells, and fibrin. PRP is enriched with various growth factors, such as Transforming Growth Factor-beta (TGF-β), Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF), Insulin-Like Growth Factor (IGF), and Vascular Endothelial Growth Factor (VEGF), all of which promote tissue growth and repair. Currently, PRP has been widely applied in the clinical field of wound repair and has achieved certain therapeutic effects. Biomaterials, as an important direction in the treatment of wounds, combined with PRP, provide new possibilities to enhance the regenerative repair of wounds by PRP. This article reviews the latest research progress of biomaterials combined with PRP in the treatment of wounds, aiming to provide references for PRP wound treatment, as well as to provide ideas for the development of subsequent medical materials.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"3961-3976"},"PeriodicalIF":6.6,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795346","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}
引用次数: 0
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International Journal of Nanomedicine
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