Pub Date : 2023-12-27DOI: 10.1016/j.nano.2023.102731
Julia Werner MSc , Florian Umstätter PhD , Tobias Hertlein PhD , Barbro Beijer PhD , Christian Kleist PhD , Eric Mühlberg MSc , Stefan Zimmermann MD , Uwe Haberkorn MD , Knut Ohlsen PhD , Gert Fricker PhD , Walter Mier PhD , Philipp Uhl PhD
Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With the vancomycin derivative FU002, we recently reported a highly potent substance active against Gram-positive bacteria with the potential to overcome vancomycin resistance. However, the translation of its excellent antimicrobial activity into clinical efficiency could be hampered by its rapid elimination from the blood stream. To improve its pharmacokinetics, we encapsulated FU002 in PEGylated liposomes. For PEG-liposomal FU002, no relevant cytotoxicity on liver, kidney and red blood cells was observed. Studies in Wistar rats revealed a significantly prolonged blood circulation of the liposomal antibiotic. In microdilution assays it could be demonstrated that encapsulation does not diminish the antimicrobial activity against staphylococci and enterococci. Highlighting its great potency, liposomal FU002 exhibited a superior therapeutic efficacy when compared to the free form in a Galleria mellonella larvae infection model.
{"title":"Improved pharmacokinetics and enhanced efficacy of the vancomycin derivative FU002 using a liposomal nanocarrier","authors":"Julia Werner MSc , Florian Umstätter PhD , Tobias Hertlein PhD , Barbro Beijer PhD , Christian Kleist PhD , Eric Mühlberg MSc , Stefan Zimmermann MD , Uwe Haberkorn MD , Knut Ohlsen PhD , Gert Fricker PhD , Walter Mier PhD , Philipp Uhl PhD","doi":"10.1016/j.nano.2023.102731","DOIUrl":"10.1016/j.nano.2023.102731","url":null,"abstract":"<div><p>Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With the vancomycin derivative FU002, we recently reported a highly potent substance active against Gram-positive bacteria with the potential to overcome vancomycin resistance. However, the translation of its excellent antimicrobial activity into clinical efficiency could be hampered by its rapid elimination from the blood stream. To improve its pharmacokinetics, we encapsulated FU002 in PEGylated liposomes. For PEG-liposomal FU002, no relevant cytotoxicity on liver, kidney and red blood cells was observed. Studies in Wistar rats revealed a significantly prolonged blood circulation of the liposomal antibiotic. In microdilution assays it could be demonstrated that encapsulation does not diminish the antimicrobial activity against staphylococci and enterococci. Highlighting its great potency, liposomal FU002 exhibited a superior therapeutic efficacy when compared to the free form in a <em>Galleria mellonella</em> larvae infection model.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"56 ","pages":"Article 102731"},"PeriodicalIF":5.4,"publicationDate":"2023-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000825/pdfft?md5=6d7933ff6822d44856d4b5da0e044201&pid=1-s2.0-S1549963423000825-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139070405","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 : 2023-12-05DOI: 10.1016/j.nano.2023.102728
Chi-Hua Lee PhD , Jenny Mac PhD , Taylor Hanley PhD , Shamima Zaman MS , Raviraj Vankayala PhD , Bahman Anvari PhD
Cytoreductive surgery remains as the gold standard to treat ovarian cancer, but with limited efficacy since not all tumors can be intraoperatively visualized for resection. We have engineered erythrocyte-derived nano-constructs that encapsulate the near infrared (NIR) fluorophore, indocyanine green (ICG), as optical probes for NIR fluorescence imaging of ovarian tumors. Herein, we have enriched the membrane of these nano-constructs with cholesterol, and functionalized their surface with folic acid (FA) to target the folate receptor-α. Using a mouse model, we show that the average fraction of the injected dose per tumor mass for nano-constructs with both membrane cholesterol enrichment and FA functionalization was ~ sixfold higher than non-encapsulated ICG, ~ twofold higher than nano-constructs enriched with cholesterol alone, and 33 % higher than nano-constructs with only FA functionalization at 24-h post-injection. These results suggest that erythrocyte-derived nano-constructs containing both cholesterol and FA present a platform for improved fluorescence imaging of ovarian tumors.
{"title":"Membrane cholesterol enrichment and folic acid functionalization lead to increased accumulation of erythrocyte-derived optical nano-constructs within the ovarian intraperitoneal tumor implants in mice","authors":"Chi-Hua Lee PhD , Jenny Mac PhD , Taylor Hanley PhD , Shamima Zaman MS , Raviraj Vankayala PhD , Bahman Anvari PhD","doi":"10.1016/j.nano.2023.102728","DOIUrl":"10.1016/j.nano.2023.102728","url":null,"abstract":"<div><p><span>Cytoreductive surgery remains as the gold standard to treat </span>ovarian cancer<span><span><span>, but with limited efficacy since not all tumors can be intraoperatively visualized for resection. We have engineered erythrocyte-derived nano-constructs that encapsulate the near infrared (NIR) fluorophore, </span>indocyanine green<span> (ICG), as optical probes<span> for NIR fluorescence imaging of ovarian tumors<span>. Herein, we have enriched the membrane of these nano-constructs with cholesterol, and functionalized their surface with folic acid (FA) to target the folate receptor-α. Using a mouse model, we show that the average fraction of the injected dose per tumor mass for nano-constructs with both membrane cholesterol enrichment and FA </span></span></span></span>functionalization was ~ sixfold higher than non-encapsulated ICG, ~ twofold higher than nano-constructs enriched with cholesterol alone, and 33 % higher than nano-constructs with only FA functionalization at 24-h post-injection. These results suggest that erythrocyte-derived nano-constructs containing both cholesterol and FA present a platform for improved fluorescence imaging of ovarian tumors.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"56 ","pages":"Article 102728"},"PeriodicalIF":5.4,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138525619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fracture healing is a complex interplay of molecular and cellular mechanisms lasting from days to weeks. The inflammatory phase is the first stage of fracture healing and is critical in setting the stage for successful healing. There has been growing interest in exploring the role of the immune system and novel therapeutic strategies, such as nanoparticle drug delivery systems in enhancing fracture healing. Advancements in nanotechnology have revolutionized drug delivery systems to the extent that they can modulate immune response during fracture healing by leveraging unique physiochemical properties. Therefore, understanding the intricate interactions between nanoparticle-based drug delivery systems and the immune response, specifically macrophages, is essential for therapeutic efficacy. This review provides a comprehensive overview of the relationship between the immune system and nanoparticles during fracture healing. Specifically, we highlight the influence of nanoparticle characteristics, such as size, surface properties, and composition, on macrophage activation, polarization, and subsequent immune responses.
Impact statement
This review provides valuable insights into the interplay between fracture healing, the immune system, and nanoparticle-based drug delivery systems. Understanding nanoparticle-macrophage interactions can advance the development of innovative therapeutic approaches to enhance fracture healing, improve patient outcomes, and pave the way for advancements in regenerative medicine.
{"title":"Integrating osteoimmunology and nanoparticle-based drug delivery systems for enhanced fracture healing","authors":"Baixue Xiao PhD , Emmanuela Adjei-Sowah MS , Danielle S.W. Benoit PhD","doi":"10.1016/j.nano.2023.102727","DOIUrl":"10.1016/j.nano.2023.102727","url":null,"abstract":"<div><p><span>Fracture healing is a complex </span>interplay<span><span> of molecular and cellular mechanisms lasting from days to weeks. The inflammatory phase<span> is the first stage of fracture healing and is critical in setting the stage for successful healing. There has been growing interest in exploring the role of the immune system and novel therapeutic strategies, such as nanoparticle </span></span>drug delivery systems<span> in enhancing fracture healing. Advancements in nanotechnology have revolutionized drug delivery systems to the extent that they can modulate immune response during fracture healing by leveraging unique physiochemical properties. Therefore, understanding the intricate interactions between nanoparticle-based drug delivery systems and the immune response, specifically macrophages, is essential for therapeutic efficacy. This review provides a comprehensive overview of the relationship between the immune system and nanoparticles during fracture healing. Specifically, we highlight the influence of nanoparticle characteristics, such as size, surface properties, and composition, on macrophage activation, polarization, and subsequent immune responses.</span></span></p></div><div><h3>Impact statement</h3><p>This review provides valuable insights into the interplay between fracture healing, the immune system, and nanoparticle-based drug delivery systems. Understanding nanoparticle-macrophage interactions can advance the development of innovative therapeutic approaches to enhance fracture healing, improve patient outcomes, and pave the way for advancements in regenerative medicine.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"56 ","pages":"Article 102727"},"PeriodicalIF":5.4,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-12-03DOI: 10.1016/j.nano.2023.102726
Jingjing Wei MSc , Yin Zhou MSc , Yiyan He PhD , Wentao Zhao MSc , Zhiqiang Luo PhD , Jian Yang PhD , Hongli Mao PhD , Zhongwei Gu MSc (Professor)
The pressing demand for innovative approaches to create delivery systems with heightened drug loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for biomimetic nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited protein adhesion (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.
{"title":"Customizing biomimetic surface attributes of dendritic lipopeptide nanoplatforms for extended circulation","authors":"Jingjing Wei MSc , Yin Zhou MSc , Yiyan He PhD , Wentao Zhao MSc , Zhiqiang Luo PhD , Jian Yang PhD , Hongli Mao PhD , Zhongwei Gu MSc (Professor)","doi":"10.1016/j.nano.2023.102726","DOIUrl":"10.1016/j.nano.2023.102726","url":null,"abstract":"<div><p>The pressing demand for innovative approaches to create delivery systems with heightened drug<span><span><span> loading and prolonged circulation has spurred numerous efforts, yielding some successes but accompanied by constraints. Our study proposes employing dendritic lipopeptide with precisely balanced opposing charges to extend blood residency for </span>biomimetic<span><span> nanoplatforms. Neutrally mixed-charged zwitterionic nanoparticles (NNPs) achieved a notable 19 % </span>simvastatin loading content and kept stable even after one-month storage at 4 °C. These nanoplatforms demonstrated low cytotoxicity in NIH-3T3 and L02 cells and negligible hemolysis (<5 %). NNPs inhibited </span></span>protein adhesion<span> (>95 %) from positively and negatively charged sources through surface hydration. In comparison to positively charged CNPs, NNPs demonstrated an 86 % decrease in phagocytic rate by BMDMs, highlighting their efficacy. Importantly, NNPs showed prolonged circulation compared to CNPs and free simvastatin. These findings highlight the potential of this biomimetic nanoplatform for future therapeutic applications with enhanced drug loading and circulation traits.</span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"56 ","pages":"Article 102726"},"PeriodicalIF":5.4,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138488079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-24DOI: 10.1016/j.nano.2023.102722
Natalia Navarro MSc , Anna Aviñó PhD , Òscar Domènech PhD , Jordi H. Borrell PhD , Ramon Eritja PhD , Carme Fàbrega PhD
DNA nanostructures have captured great interest as drug delivery vehicles for cancer therapy. Despite rapid progress in the field, some hurdles, such as low cellular uptake, low tissue specificity or ambiguous drug loading, remain unsolved. Herein, well-known antitumor drugs (doxorubicin, auristatin, and floxuridine) were site-specifically incorporated into DNA nanostructures, demonstrating the potential advantages of covalently linking drug molecules via structural staples instead of incorporating the drugs by noncovalent binding interactions. The covalent strategy avoids critical issues such as an unknown number of drug-DNA binding events and premature drug release. Moreover, covalently modified origami offers the possibility of precisely incorporating several synergetic antitumor drugs into the DNA nanostructure at a predefined molar ratio and to control the exact spatial orientation of drugs into DNA origami. Additionally, DNA-based nanoscaffolds have been reported to have a low intracellular uptake. Thus, two cellular uptake enhancing mechanisms were studied: the introduction of folate units covalently linked to DNA origami and the transfection of DNA origami with Lipofectamine. Importantly, both methods increased the internalization of DNA origami into HTB38 and HCC2998 colorectal cancer cells and produced greater cytotoxic activity when the DNA origami incorporated antiproliferative drugs. The results here present a successful and conceptually distinct approach for the development of DNA-based nanostructures as drug delivery vehicles, which can be considered an important step towards the development of highly precise nanomedicines.
{"title":"Defined covalent attachment of three cancer drugs to DNA origami increases cytotoxicity at nanomolar concentration","authors":"Natalia Navarro MSc , Anna Aviñó PhD , Òscar Domènech PhD , Jordi H. Borrell PhD , Ramon Eritja PhD , Carme Fàbrega PhD","doi":"10.1016/j.nano.2023.102722","DOIUrl":"10.1016/j.nano.2023.102722","url":null,"abstract":"<div><p>DNA nanostructures have captured great interest as drug delivery vehicles for cancer therapy. Despite rapid progress in the field, some hurdles, such as low cellular uptake, low tissue specificity or ambiguous drug loading, remain unsolved. Herein, well-known antitumor drugs (doxorubicin, auristatin, and floxuridine) were site-specifically incorporated into DNA nanostructures, demonstrating the potential advantages of covalently linking drug molecules via structural staples instead of incorporating the drugs by noncovalent binding interactions. The covalent strategy avoids critical issues such as an unknown number of drug-DNA binding events and premature drug release. Moreover, covalently modified origami offers the possibility of precisely incorporating several synergetic antitumor drugs into the DNA nanostructure at a predefined molar ratio and to control the exact spatial orientation of drugs into DNA origami. Additionally, DNA-based nanoscaffolds have been reported to have a low intracellular uptake. Thus, two cellular uptake enhancing mechanisms were studied: the introduction of folate units covalently linked to DNA origami and the transfection of DNA origami with Lipofectamine. Importantly, both methods increased the internalization of DNA origami into HTB38 and HCC2998 colorectal cancer cells and produced greater cytotoxic activity when the DNA origami incorporated antiproliferative drugs. The results here present a successful and conceptually distinct approach for the development of DNA-based nanostructures as drug delivery vehicles, which can be considered an important step towards the development of highly precise nanomedicines.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"55 ","pages":"Article 102722"},"PeriodicalIF":5.4,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000734/pdfft?md5=f5206ed1652e7df6acf7ac3b4487d213&pid=1-s2.0-S1549963423000734-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440968","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 : 2023-11-24DOI: 10.1016/j.nano.2023.102721
Magdalena Bamburowicz-Klimkowska PhD , Michal Bystrzejewski PhD, DSc , Artur Kasprzak PhD, DSc , Andrzej Cieszanowski MD, PhD, Prof , Ireneusz P. Grudzinski PhD, DSc, Prof
Integrin beta-3 is a cell adhesion molecule that mediate cell-to-cell and cell-to-extracellular matrix communication. The major goal of this study was to explore melanoma cells (B16F10) based upon specific direct targeting of the β3 subunit (CD61) in the integrin αvβ3 receptor using carbon-encapsulated iron nanoparticles decorated with monoclonal antibodies (Fe@C-CONH-anti-CD61 and Fe@C-(CH2)2-CONH-anti-CD61). Both melanoma cells treated with nanoparticles as well as C57BL/6 mice bearing syngeneic B16-F10 tumors intravenously injected with nanoparticles were tested in preclinical MRI studies. The as-synthesized carbon-encapsulated iron nanoparticles functionalized with CD61 monoclonal antibodies have been successfully used as a novel targeted contrast agent for MRI-based tracking melanoma cells expressing the β3 subunit of the integrin αvβ3 receptor.
{"title":"Monoclonal antibody-navigated carbon-encapsulated iron nanoparticles used for MRI-based tracking integrin receptors in murine melanoma","authors":"Magdalena Bamburowicz-Klimkowska PhD , Michal Bystrzejewski PhD, DSc , Artur Kasprzak PhD, DSc , Andrzej Cieszanowski MD, PhD, Prof , Ireneusz P. Grudzinski PhD, DSc, Prof","doi":"10.1016/j.nano.2023.102721","DOIUrl":"10.1016/j.nano.2023.102721","url":null,"abstract":"<div><p><span><span><span>Integrin beta-3 is a </span>cell adhesion molecule<span> that mediate cell-to-cell and cell-to-extracellular matrix communication. The major goal of this study was to explore melanoma cells (B16F10) based upon specific direct targeting of the β3 subunit (CD61) in the integrin αvβ3 receptor using carbon-encapsulated iron </span></span>nanoparticles<span> decorated with monoclonal antibodies (Fe@C-CONH-anti-CD61 and Fe@C-(CH</span></span><sub>2</sub>)<sub>2</sub><span><span>-CONH-anti-CD61). Both melanoma cells treated with nanoparticles as well as C57BL/6 mice bearing syngeneic B16-F10 tumors intravenously injected with nanoparticles were tested in preclinical MRI studies. The as-synthesized carbon-encapsulated iron nanoparticles functionalized with </span>CD61 monoclonal antibodies have been successfully used as a novel targeted contrast agent for MRI-based tracking melanoma cells expressing the β3 subunit of the integrin αvβ3 receptor.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"55 ","pages":"Article 102721"},"PeriodicalIF":5.4,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-23DOI: 10.1016/j.nano.2023.102723
Shuyi Li MSc , Qian Yuan MSc , Minghui Yang BSc , Xinyi Long BSc , Jianwu Sun MSc , Xin Yuan BSc , Lang Liu BSc , Wanting Zhang BSc , Quanjiang Li BSc , Zhujie Deng BSc , Rui Tian BSc , Renhao Xu BSc , Lingna Xie MSc , Jingna Yuan BSc , Yue He MD , Yi Liu MD , Hongmei Liu MD , Zhengqiang Yuan PhD
Objective
Osteoarthritis (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs.
Materials and methods
MSC-EVs were isolated from sodium alginate (SA) and hyaluronic acid (HA) composite hydrogel (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo.
Results
EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers.
Conclusion
The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.
目的:骨关节炎(OA)的特点是进行性软骨变性和缺乏根治性治疗。因此,迫切需要更有效的治疗方法。间充质干细胞(MSCs)衍生的细胞外囊泡(EVs)和淫羊藿苷(ICA)在软骨缺损的修复中都有很好的应用前景。本研究提出ICA可能联合增强msc - ev的软骨修复能力。材料和方法:从海藻酸钠(SA)和透明质酸(HA)复合水凝胶(SA-HA)细胞球体培养中分离出msc - ev。采用SA-HA水凝胶联合ev和ICA,观察其对软骨缺损的体内治疗效果。结果:EVs和ICA在促进MSCs和炎性软骨细胞增殖和迁移方面具有协同作用。联合治疗显著增强了大鼠软骨缺损的修复,其机制涉及软骨降解和合成因子的伴随调节。结论:msc - ev - ica /SA-HA水凝胶是一种治疗骨性关节炎软骨缺损的新方法。
{"title":"Enhanced cartilage regeneration by icariin and mesenchymal stem cell-derived extracellular vesicles combined in alginate-hyaluronic acid hydrogel","authors":"Shuyi Li MSc , Qian Yuan MSc , Minghui Yang BSc , Xinyi Long BSc , Jianwu Sun MSc , Xin Yuan BSc , Lang Liu BSc , Wanting Zhang BSc , Quanjiang Li BSc , Zhujie Deng BSc , Rui Tian BSc , Renhao Xu BSc , Lingna Xie MSc , Jingna Yuan BSc , Yue He MD , Yi Liu MD , Hongmei Liu MD , Zhengqiang Yuan PhD","doi":"10.1016/j.nano.2023.102723","DOIUrl":"10.1016/j.nano.2023.102723","url":null,"abstract":"<div><h3>Objective</h3><p><span>Osteoarthritis<span> (OA) is characterized by progressive cartilage degeneration and absence of curative therapies. Therefore, more efficient therapies are compellingly needed. Both </span></span>mesenchymal stem cells<span> (MSCs)-derived extracellular vesicles (EVs) and Icariin (ICA) are promising for repair of cartilage defect. This study proposes that ICA may be combined to potentiate the cartilage repair capacity of MSC-EVs.</span></p></div><div><h3>Materials and methods</h3><p><span>MSC-EVs were isolated from sodium alginate<span> (SA) and hyaluronic acid (HA) </span></span>composite hydrogel<span> (SA-HA) cell spheroid culture. EVs and ICA were combined in SA-HA hydrogel to test therapeutic efficacy on cartilage defect in vivo.</span></p></div><div><h3>Results</h3><p>EVs and ICA were synergistic for promoting both proliferation and migration of MSCs and inflammatory chondrocytes. The combination therapy led to strikingly enhanced repair on cartilage defect in rats, with mechanisms involved in the concomitant modulation of both cartilage degradation and synthesis makers.</p></div><div><h3>Conclusion</h3><p>The MSC-EVs-ICA/SA-HA hydrogel potentially constitutes a novel therapy for cartilage defect in OA.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"55 ","pages":"Article 102723"},"PeriodicalIF":5.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-23DOI: 10.1016/j.nano.2023.102720
Estefanía Lozano-Andrés PhD , Tina Van Den Broeck PhD , Lili Wang PhD , Majid Mehrpouyan PhD , Ye Tian PhD , Xiaomei Yan PhD , Ger J.A. Arkesteijn PhD , Marca H.M. Wauben PhD
Flow cytometry allows to characterize nanoparticles (NPs) and extracellular vesicles (EVs) but results are often expressed in arbitrary units of fluorescence. We evaluated the precision and accuracy of molecules of equivalent soluble fluorophores (MESF) beads for calibration of NPs and EVs. Firstly, two FITC-MESF bead sets, 2 and 6 um in size, were measured on three flow cytometers. We showed that arbitrary units could not be compared between instruments but after calibration, comparable FITC MESF units were achieved. However, the two calibration bead sets displayed varying slopes that were consistent across platforms.
Further investigation revealed that the intrinsic uncertainty related to the MESF beads impacts the robust assignment of values to NPs and EVs based on extrapolation into the dim fluorescence range. Similar variations were found with PE MESF calibration.
Therefore, the same calibration materials and numbers of calibration points should be used for reliable comparison of submicron sized particles.
{"title":"Intrinsic variability of fluorescence calibrators impacts the assignment of MESF or ERF values to nanoparticles and extracellular vesicles by flow cytometry","authors":"Estefanía Lozano-Andrés PhD , Tina Van Den Broeck PhD , Lili Wang PhD , Majid Mehrpouyan PhD , Ye Tian PhD , Xiaomei Yan PhD , Ger J.A. Arkesteijn PhD , Marca H.M. Wauben PhD","doi":"10.1016/j.nano.2023.102720","DOIUrl":"10.1016/j.nano.2023.102720","url":null,"abstract":"<div><p>Flow cytometry allows to characterize nanoparticles (NPs) and extracellular vesicles (EVs) but results are often expressed in arbitrary units of fluorescence. We evaluated the precision and accuracy of molecules of equivalent soluble fluorophores (MESF) beads for calibration of NPs and EVs. Firstly, two FITC-MESF bead sets, 2 and 6 um in size, were measured on three flow cytometers. We showed that arbitrary units could not be compared between instruments but after calibration, comparable FITC MESF units were achieved. However, the two calibration bead sets displayed varying slopes that were consistent across platforms.</p><p>Further investigation revealed that the intrinsic uncertainty related to the MESF beads impacts the robust assignment of values to NPs and EVs based on extrapolation into the dim fluorescence range. Similar variations were found with PE MESF calibration.</p><p>Therefore, the same calibration materials and numbers of calibration points should be used for reliable comparison of submicron sized particles.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"56 ","pages":"Article 102720"},"PeriodicalIF":5.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000710/pdfft?md5=7ce6e8120251cac93c9d5492d02b8d27&pid=1-s2.0-S1549963423000710-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440971","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 : 2023-11-23DOI: 10.1016/j.nano.2023.102724
Isabel Quint MSc , Jonathan Simantzik MSc , Lars Kaiser PhD , Stefan Laufer PhD , Rene' Csuk PhD , David Smith PhD , Matthias Kohl PhD , Hans-Peter Deigner PhD
In recent decades, nanopores have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance, as their detection is difficult or expensive using available methods such as HPLC or LC-MS. DNA aptamers are an excellent detection element for sensitive and specific detection of small molecules. Herein, a method for quantifying small molecules using a ready-to-use sequencing platform is described.
Taking ethanolamine as an example, a strand displacement assay is developed in which the target-binding aptamer is displaced from the surface of magnetic particles by ethanolamine. Non-displaced aptamer and thus the ethanolamine concentration are detected by the nanopore system and can be quantified in the micromolar range using our in-house developed analysis software. This method is thus the first to describe a label-free approach for the detection of small molecules in a protein nanopore system.
{"title":"Ready-to-use nanopore platform for label-free small molecule quantification: Ethanolamine as first example","authors":"Isabel Quint MSc , Jonathan Simantzik MSc , Lars Kaiser PhD , Stefan Laufer PhD , Rene' Csuk PhD , David Smith PhD , Matthias Kohl PhD , Hans-Peter Deigner PhD","doi":"10.1016/j.nano.2023.102724","DOIUrl":"10.1016/j.nano.2023.102724","url":null,"abstract":"<div><p><span>In recent decades, nanopores<span> have become a promising diagnostic tool. Protein and solid-state nanopores are increasingly used for both RNA/DNA sequencing and small molecule detection. The latter is of great importance, as their detection is difficult or expensive using available methods such as </span></span>HPLC<span><span> or LC-MS. DNA </span>aptamers are an excellent detection element for sensitive and specific detection of small molecules. Herein, a method for quantifying small molecules using a ready-to-use sequencing platform is described.</span></p><p>Taking ethanolamine as an example, a strand displacement assay is developed in which the target-binding aptamer is displaced from the surface of magnetic particles by ethanolamine. Non-displaced aptamer and thus the ethanolamine concentration are detected by the nanopore system and can be quantified in the micromolar range using our in-house developed analysis software. This method is thus the first to describe a label-free approach for the detection of small molecules in a protein nanopore system.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"55 ","pages":"Article 102724"},"PeriodicalIF":5.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-23DOI: 10.1016/j.nano.2023.102725
Mengmeng Zhao MD , Jialing Guo PhD , Chaoying Tian MD , Mei Yan MD , Yingying Zhou MD , Chenxin Liu MD , Mengxue Pang MD , Bin Du Prof , Genyang Cheng Prof
Mitochondrial oxidative stress and inflammation are the main pathological features of acute kidney injury (AKI). However, systemic toxicity of anti-inflammatory drugs and low bioavailability of antioxidants limit the treatment of AKI. Here, the lipid micelle nanosystem modified with l-serine was designed to improve treatment of AKI. The micelle kernels coating the antioxidant drug 4-carboxybutyl triphenylph-osphine bromide-modified curcumin (Cur-TPP) and quercetin (Que). In the cisplatin (CDDP)-induced AKI model, the nanosystem protected mitochondrial structure and improved renal function. Compared to mono-targeted group, the mitochondrial ROS content of renal tubular epithelial cells acting in the dual-target group decreased about 1.66-fold in vitro, serum creatinine (Scr) and urea nitrogen (BUN) levels were reduced by 1.5 and 1.2 mmol/L in vivo, respectively. Mechanistic studies indicated that the nanosystem inhibited the inflammatory response by interfering with the NF-κB and Nrf2 pathways. This study provides an efficient and low-toxicity strategy for AKI therapy.
{"title":"Dual-targeted nanoparticles with removing ROS inside and outside mitochondria for acute kidney injury treatment","authors":"Mengmeng Zhao MD , Jialing Guo PhD , Chaoying Tian MD , Mei Yan MD , Yingying Zhou MD , Chenxin Liu MD , Mengxue Pang MD , Bin Du Prof , Genyang Cheng Prof","doi":"10.1016/j.nano.2023.102725","DOIUrl":"10.1016/j.nano.2023.102725","url":null,"abstract":"<div><p><span><span>Mitochondrial oxidative stress and inflammation are the main pathological features of </span>acute kidney injury<span> (AKI). However, systemic toxicity of anti-inflammatory drugs and low bioavailability of antioxidants limit the treatment<span><span> of AKI. Here, the lipid<span> micelle </span></span>nanosystem modified with </span></span></span><span>l</span><span><span><span><span>-serine was designed to improve treatment of AKI. The micelle kernels coating the antioxidant drug 4-carboxybutyl triphenylph-osphine bromide-modified </span>curcumin<span><span> (Cur-TPP) and quercetin (Que). In the </span>cisplatin (CDDP)-induced AKI model, the nanosystem protected mitochondrial structure and improved </span></span>renal function<span>. Compared to mono-targeted group, the mitochondrial ROS content of renal tubular epithelial cells acting in the dual-target group decreased about 1.66-fold in vitro, </span></span>serum creatinine (Scr) and urea nitrogen (BUN) levels were reduced by 1.5 and 1.2 mmol/L in vivo, respectively. Mechanistic studies indicated that the nanosystem inhibited the inflammatory response by interfering with the NF-κB and Nrf2 pathways. This study provides an efficient and low-toxicity strategy for AKI therapy.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":"55 ","pages":"Article 102725"},"PeriodicalIF":5.4,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}