Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor survival rates. Here, we evaluated iron-doped hydroxyapatite (FeHA) as a potential nanomedicine-based approach to combat PDAC. FeHA, in combination with a sublethal dose of the glutathione peroxidase 4 (GPX4) inhibitor RSL3, was found to trigger ferroptosis in KRAS mutant PANC-1 cells, but not in BxPC3 cells, while sparing normal human cells (fibroblasts and peripheral blood mononuclear cells). These findings were recapitulated in 3D spheroids generated using PDAC cells harboring wild-type versus mutant KRAS. Moreover, ferroptosis induction by FeHA plus RSL3 was reversed by the knockdown of STEAP3, a metalloreductase responsible for converting Fe3+ to Fe2+. Taken together, our data show that FeHA is capable of triggering cancer cell death in a KRAS-selective, STEAP3-dependent manner in PDAC cells.
{"title":"Exploiting the ferroaddiction of pancreatic cancer cells using Fe-doped nanoparticles","authors":"Thanpisit Lomphithak M.Sc. , Apiwit Sae-Fung M.Sc. , Simone Sprio Ph.D. , Anna Tampieri Ph.D. , Siriporn Jitkaew Ph.D. , Bengt Fadeel M.D., Ph.D.","doi":"10.1016/j.nano.2023.102714","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102714","url":null,"abstract":"<div><p>Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor survival rates. Here, we evaluated iron-doped hydroxyapatite (FeHA) as a potential nanomedicine-based approach to combat PDAC. FeHA, in combination with a sublethal dose of the glutathione peroxidase 4 (GPX4) inhibitor RSL3, was found to trigger ferroptosis in <em>KRAS</em> mutant PANC-1 cells, but not in BxPC3 cells, while sparing normal human cells (fibroblasts and peripheral blood mononuclear cells). These findings were recapitulated in 3D spheroids generated using PDAC cells harboring wild-type <em>versus</em> mutant <em>KRAS</em>. Moreover, ferroptosis induction by FeHA plus RSL3 was reversed by the knockdown of STEAP3, a metalloreductase responsible for converting Fe<sup>3+</sup> to Fe<sup>2+</sup>. Taken together, our data show that FeHA is capable of triggering cancer cell death in a <em>KRAS</em>-selective, STEAP3-dependent manner in PDAC cells.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92055142","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 : 2023-10-29DOI: 10.1016/j.nano.2023.102715
Marco Felipe Salas-Orozco PhD , Ana Cecilia Lorenzo-Leal PhD , Idania de Alba Montero PhD , Nuria Patiño Marín PhD , Miguel Angel Casillas Santana PhD , Horacio Bach PhD
The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.
{"title":"Mechanism of escape from the antibacterial activity of metal-based nanoparticles in clinically relevant bacteria: A systematic review","authors":"Marco Felipe Salas-Orozco PhD , Ana Cecilia Lorenzo-Leal PhD , Idania de Alba Montero PhD , Nuria Patiño Marín PhD , Miguel Angel Casillas Santana PhD , Horacio Bach PhD","doi":"10.1016/j.nano.2023.102715","DOIUrl":"10.1016/j.nano.2023.102715","url":null,"abstract":"<div><p>The emergency of antibiotic-resistant bacteria in severe infections is increasing, especially in nosocomial environments. The ESKAPE group is of special importance in the groups of multi-resistant bacteria due to its high capacity to generate resistance to antibiotics and bactericides. Therefore, metal-based nanomaterials are an attractive alternative to combat them because they have been demonstrated to damage biomolecules in the bacterial cells. However, there is a concern about bacteria developing resistance to NPs and their harmful effects due to environmental accumulation. Therefore, this systematic review aims to report the clinically relevant bacteria that have developed resistance to the NPs. According to the results of this systematic review, various mechanisms to counteract the antimicrobial activity of various NP types have been proposed. These mechanisms can be grouped into the following categories: production of extracellular compounds, metal efflux pumps, ROS response, genetic changes, DNA repair, adaptative morphogenesis, and changes in the plasma membrane.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425176","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 : 2023-09-01DOI: 10.1016/j.nano.2023.102700
Aiai Zhang MD , Kaijing Liu PhD , Xiaoyu Liang PhD , Huiyang Li PhD , Xue Fu PhD , Ni Zhu MD , Fangjiang Li BS , Jing Yang PhD
Arterial injury makes the tissue in a state of high oxidative stress. At the same time, abnormal lipid metabolism can further lead to bleeding and thrombosis. Therefore, the anti-inflammatory and anti-oxidant polyphenol, EGCG was organically complexed with Fe3+ to form a metal-phenolic framework carrier. And the antihyperlipidemic drug, atorvastatin (ATV) was loaded into the carrier to enhance the bioavailability, and simultaneously alleviate the oxidative stress of the inflammatory site and abnormal lipid metabolism. The results confirmed that the obtained material EGCG-Fe-ATV had good biocompatibility and biosafety effect. In addition, EGCG-Fe-ATV showed outstanding anti-inflammatory, anti-oxidant and lipid-lowering properties. These therapeutic outcomes of EGCG-Fe-ATV were achieved by reducing systemic and local oxidative stress and inflammation, alleviating inflammatory cell infiltration in plaques, and modulating lipid synthesis and transferase to alter cholesterol transport. In conclusion, the combination of metal-phenolic capsules with ATV provides a new strategy for reshaping the oxidative microenvironment of atherosclerosis.
{"title":"Metal-phenolic capsules with ROS scavenging reshape the oxidative microenvironment of atherosclerosis","authors":"Aiai Zhang MD , Kaijing Liu PhD , Xiaoyu Liang PhD , Huiyang Li PhD , Xue Fu PhD , Ni Zhu MD , Fangjiang Li BS , Jing Yang PhD","doi":"10.1016/j.nano.2023.102700","DOIUrl":"10.1016/j.nano.2023.102700","url":null,"abstract":"<div><p><span>Arterial injury<span><span> makes the tissue in a state of high oxidative stress. At the same time, abnormal </span>lipid metabolism<span> can further lead to bleeding and thrombosis. Therefore, the anti-inflammatory and anti-oxidant polyphenol, EGCG was organically complexed with Fe</span></span></span><sup>3+</sup><span><span><span> to form a metal-phenolic framework carrier. And the antihyperlipidemic drug, </span>atorvastatin<span> (ATV) was loaded into the carrier to enhance the bioavailability, and simultaneously alleviate the oxidative stress of the inflammatory site and abnormal lipid<span> metabolism. The results confirmed that the obtained material EGCG-Fe-ATV had good biocompatibility and biosafety effect. In addition, EGCG-Fe-ATV showed outstanding anti-inflammatory, anti-oxidant and lipid-lowering properties. These therapeutic outcomes of EGCG-Fe-ATV were achieved by reducing systemic and local oxidative stress and inflammation, alleviating </span></span></span>inflammatory cell<span><span><span> infiltration in plaques, and modulating </span>lipid synthesis<span> and transferase<span> to alter cholesterol transport. In conclusion, the combination of metal-phenolic capsules<span> with ATV provides a new strategy for reshaping the oxidative microenvironment of </span></span></span></span>atherosclerosis.</span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9981744","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 : 2023-09-01DOI: 10.1016/j.nano.2023.102706
Zozan Guleken PhD , Zeynep Ceylan PhD , Aynur Aday PhD , Ayşe Gül Bayrak PhD , İpek Yönal Hindilerden MD, Prof. , Meliha Nalçacı MD, Prof. , Paweł Jakubczyk Prof. , Dorota Jakubczyk PhD , Monika Kula-Maximenko PhD , Joanna Depciuch PhD
Primary myelofibrosis (PM) is one of the myeloproliferative neoplasm, where stem cell-derived clonal neoplasms was noticed. Diagnosis of this disease is based on: physical examination, peripheral blood findings, bone marrow morphology, cytogenetics, and molecular markers. However, the molecular marker of PM, which is a mutation in the JAK2V617F gene, was observed also in other myeloproliferative neoplasms such as polycythemia vera and essential thrombocythemia. Therefore, there is a need to find methods that provide a marker unique to PM and allow for higher accuracy of PM diagnosis and consequently the treatment of the disease. Continuing, in this study, we used Raman spectroscopy, Principal Components Analysis (PCA), and Partial Least Squares (PLS) analysis as helpful diagnostic tools for PM. Consequently, we used serum collected from PM patients, which were classified using clinical parameters of PM such as the dynamic international prognostic scoring system (DIPSS) for primary myelofibrosis plus score, the JAK2V617F mutation, spleen size, bone marrow reticulin fibrosis degree and use of hydroxyurea drug features. Raman spectra showed higher amounts of C-H, C-C and C-C/C-N and amide II and lower amounts of amide I and vibrations of CH3 groups in PM patients than in healthy ones. Furthermore, shifts of amides II and I vibrations in PM patients were noticed. Machine learning methods were used to analyze Raman regions: (i) 800 cm−1 and 1800 cm−1, (ii) 1600 cm−1–1700 cm−1, and (iii) 2700 cm−1–3000 cm−1 showed 100 % accuracy, sensitivity, and specificity. Differences in the spectral dynamic showed that differences in the amide II and amide I regions were the most significant in distinguishing between PM and healthy subjects. Importantly, until now, the efficacy of Raman spectroscopy has not been established in clinical diagnostics of PM disease using the correlation between Raman spectra and PM clinical prognostic scoring. Continuing, our results showed the correlation between Raman signals and bone marrow fibrosis, as well as JAKV617F. Consequently, the results revealed that Raman spectroscopy has a high potential for use in medical laboratory diagnostics to quantify multiple biomarkers simultaneously, especially in the selected Raman regions.
{"title":"Detection of primary myelofibrosis in blood serum via Raman spectroscopy assisted by machine learning approaches; correlation with clinical diagnosis","authors":"Zozan Guleken PhD , Zeynep Ceylan PhD , Aynur Aday PhD , Ayşe Gül Bayrak PhD , İpek Yönal Hindilerden MD, Prof. , Meliha Nalçacı MD, Prof. , Paweł Jakubczyk Prof. , Dorota Jakubczyk PhD , Monika Kula-Maximenko PhD , Joanna Depciuch PhD","doi":"10.1016/j.nano.2023.102706","DOIUrl":"10.1016/j.nano.2023.102706","url":null,"abstract":"<div><p><span><span><span>Primary myelofibrosis<span> (PM) is one of the myeloproliferative neoplasm, where stem cell-derived clonal neoplasms was noticed. Diagnosis of this disease is based on: physical examination, peripheral blood findings, bone marrow morphology, cytogenetics, and </span></span>molecular markers<span><span>. However, the molecular marker of PM, which is a mutation in the JAK2V617F gene, was observed also in other myeloproliferative neoplasms such as polycythemia vera<span> and essential thrombocythemia. Therefore, there is a need to find methods that provide a marker unique to PM and allow for higher accuracy of PM diagnosis and consequently the </span></span>treatment<span><span><span> of the disease. Continuing, in this study, we used Raman spectroscopy, </span>Principal Components Analysis<span> (PCA), and Partial Least Squares (PLS) analysis as helpful diagnostic tools for PM. Consequently, we used serum collected from PM patients, which were classified using clinical parameters of PM such as the dynamic </span></span>international prognostic scoring system<span><span> (DIPSS) for primary myelofibrosis plus score, the JAK2V617F mutation, spleen size, bone marrow </span>reticulin<span> fibrosis degree and use of </span></span></span></span></span>hydroxyurea<span><span> drug features. </span>Raman spectra showed higher amounts of C-H, C-C and C-C/C-N and amide II and lower amounts of amide I and vibrations of CH</span></span><sub>3</sub><span> groups in PM patients than in healthy ones. Furthermore, shifts of amides<span> II and I vibrations in PM patients were noticed. Machine learning methods were used to analyze Raman regions: (i) 800 cm</span></span><sup>−1</sup> and 1800 cm<sup>−1</sup>, (ii) 1600 cm<sup>−1</sup>–1700 cm<sup>−1</sup>, and (iii) 2700 cm<sup>−1</sup>–3000 cm<sup>−1</sup><span> showed 100 % accuracy, sensitivity, and specificity. Differences in the spectral dynamic showed that differences in the amide II and amide I regions were the most significant in distinguishing between PM and healthy subjects. Importantly, until now, the efficacy of Raman spectroscopy has not been established in clinical diagnostics of PM disease using the correlation between Raman spectra and PM clinical prognostic scoring. Continuing, our results showed the correlation between Raman signals and bone marrow fibrosis, as well as JAKV617F. Consequently, the results revealed that Raman spectroscopy has a high potential for use in medical laboratory diagnostics to quantify multiple biomarkers simultaneously, especially in the selected Raman regions.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10522993","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 : 2023-09-01DOI: 10.1016/j.nano.2023.102699
Clara Manesco MSc , Oscar Saavedra-Villanueva PhD , Marta Martin PhD , Joshua de Lizaraga MSc , Béla Varga PhD , Thierry Cloitre PhD , Yannick Nicolas Gerber PhD , Florence Evelyne Perrin Prof. , Csilla Gergely Prof.
Spinal cord injury is a dramatic disease leading to severe motor, sensitive and autonomic impairments. After injury the axonal regeneration is partly inhibited by the glial scar, acting as a physical and chemical barrier. The scarring process involves microglia, astrocytes and extracellular matrix components, such as collagen, constructing the fibrotic component of the scar. To investigate the role of collagen, we used a multimodal label-free imaging approach combining multiphoton and atomic force microscopy. The second harmonic generation signal exhibited by fibrillar collagen enabled to specifically monitor it as a biomarker of the lesion. An increase in collagen density and the formation of more tortuous fibers over time after injury are observed. Nano-mechanical investigations revealed a noticeable hardening of the injured area, correlated with collagen fibers' formation. These observations indicate the concomitance of important structural and mechanical modifications during the fibrotic scar evolution.
{"title":"Organization of collagen fibers and tissue hardening: Markers of fibrotic scarring after spinal cord injury in mice revealed by multiphoton-atomic force microscopy imaging","authors":"Clara Manesco MSc , Oscar Saavedra-Villanueva PhD , Marta Martin PhD , Joshua de Lizaraga MSc , Béla Varga PhD , Thierry Cloitre PhD , Yannick Nicolas Gerber PhD , Florence Evelyne Perrin Prof. , Csilla Gergely Prof.","doi":"10.1016/j.nano.2023.102699","DOIUrl":"10.1016/j.nano.2023.102699","url":null,"abstract":"<div><p><span><span>Spinal cord injury is a dramatic disease leading to severe motor, sensitive and </span>autonomic<span><span> impairments. After injury the axonal regeneration is partly inhibited by the </span>glial scar, acting as a physical and chemical barrier. The scarring process involves </span></span>microglia<span><span><span>, astrocytes and extracellular matrix components, such as collagen, constructing the fibrotic component of the scar. To investigate the role of collagen, we used a multimodal label-free imaging approach combining multiphoton and </span>atomic force microscopy<span>. The second harmonic generation signal exhibited by </span></span>fibrillar collagen enabled to specifically monitor it as a biomarker of the lesion. An increase in collagen density and the formation of more tortuous fibers over time after injury are observed. Nano-mechanical investigations revealed a noticeable hardening of the injured area, correlated with collagen fibers' formation. These observations indicate the concomitance of important structural and mechanical modifications during the fibrotic scar evolution.</span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10064900","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 : 2023-09-01DOI: 10.1016/j.nano.2023.102705
Troy A. Halseth PhD , Adele B. Correia BS , Mark L. Schultz PhD , Maria V. Fawaz PhD , Esmée Q. Kuiper BS , Preethi Kumaran BS , Kristen Hong Dorsey MS , Edward H. Schuchman PhD , Andrew P. Lieberman MD,PhD , Anna Schwendeman PhD
Acid sphingomyelinase deficiency (ASMD) is a severe lipid storage disorder caused by the diminished activity of the acid sphingomyelinase enzyme. ASMD is characterized by the accumulation of sphingomyelin in late endosomes and lysosomes leading to progressive neurological dysfunction and hepatosplenomegaly. Our objective was to investigate the utility of synthetic apolipoprotein A-I (ApoA-I) mimetics designed to act as lipid scavengers for the treatment of ASMD. We determined the lead peptide, 22A, could reduce sphingomyelin accumulation in ASMD patient skin fibroblasts in a dose dependent manner. Intraperitoneal administration of 22A formulated as a synthetic high-density lipoprotein (sHDL) nanodisc mobilized sphingomyelin from peripheral tissues into circulation and improved liver function in a mouse model of ASMD. Together, our data demonstrates that apolipoprotein mimetics could serve as a novel therapeutic strategy for modulating the pathology observed in ASMD.
{"title":"Apolipoprotein-mimetic nanodiscs reduce lipid accumulation and improve liver function in acid sphingomyelinase deficiency","authors":"Troy A. Halseth PhD , Adele B. Correia BS , Mark L. Schultz PhD , Maria V. Fawaz PhD , Esmée Q. Kuiper BS , Preethi Kumaran BS , Kristen Hong Dorsey MS , Edward H. Schuchman PhD , Andrew P. Lieberman MD,PhD , Anna Schwendeman PhD","doi":"10.1016/j.nano.2023.102705","DOIUrl":"10.1016/j.nano.2023.102705","url":null,"abstract":"<div><p><span><span>Acid sphingomyelinase deficiency (ASMD) is a severe </span>lipid<span> storage disorder caused by the diminished activity of the acid sphingomyelinase enzyme. ASMD is characterized by the accumulation of </span></span>sphingomyelin<span> in late endosomes and lysosomes<span><span> leading to progressive neurological dysfunction and hepatosplenomegaly<span>. Our objective was to investigate the utility of synthetic apolipoprotein A-I (ApoA-I) mimetics designed to act as lipid scavengers for the </span></span>treatment<span><span> of ASMD. We determined the lead peptide, 22A, could reduce sphingomyelin accumulation in ASMD patient skin fibroblasts<span> in a dose dependent manner. Intraperitoneal administration of 22A formulated as a synthetic high-density lipoprotein (sHDL) </span></span>nanodisc mobilized sphingomyelin from peripheral tissues into circulation and improved liver function in a mouse model of ASMD. Together, our data demonstrates that apolipoprotein mimetics could serve as a novel therapeutic strategy for modulating the pathology observed in ASMD.</span></span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10145234","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 : 2023-09-01DOI: 10.1016/j.nano.2023.102703
Sylwia Michlewska PhD , Dagmara Wójkowska PhD , Cezary Watala Professor , Elżbieta Skiba PhD , Paula Ortega Professor , Francisco Javier de la Mata Professor , Maria Bryszewska Professor , Maksim Ionov Professor
Carbosilane metallodendrimers, based on the arene Ru(II) complex (CRD13) and integrated to imino-pyridine surface groups have been investigated as an anticancer agent in a mouse model with triple-negative breast cancer. The dendrimer entered into the cells efficiently, and exhibited selective toxicity for 4T1 cells. In vivo investigations proved that a local injection of CRD13 caused a reduction of tumour mass and was non-toxic. ICP analyses indicated that Ru(II) accumulated in all tested tissues with a greater content detected in the tumour.
{"title":"Ruthenium metallodendrimer against triple-negative breast cancer in mice","authors":"Sylwia Michlewska PhD , Dagmara Wójkowska PhD , Cezary Watala Professor , Elżbieta Skiba PhD , Paula Ortega Professor , Francisco Javier de la Mata Professor , Maria Bryszewska Professor , Maksim Ionov Professor","doi":"10.1016/j.nano.2023.102703","DOIUrl":"10.1016/j.nano.2023.102703","url":null,"abstract":"<div><p>Carbosilane metallodendrimers, based on the arene Ru(II) complex (<strong>CRD13</strong>) and integrated to imino-pyridine surface groups have been investigated as an anticancer agent in a mouse model with triple-negative breast cancer. The dendrimer entered into the cells efficiently, and exhibited selective toxicity for 4T1 cells. <em>In vivo</em> investigations proved that a local injection of <strong>CRD13</strong> caused a reduction of tumour mass and was non-toxic. ICP analyses indicated that Ru(II) accumulated in all tested tissues with a greater content detected in the tumour.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000540/pdfft?md5=910f44dfd820b4b18cc03e60680c80ec&pid=1-s2.0-S1549963423000540-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10081397","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 : 2023-09-01DOI: 10.1016/j.nano.2023.102693
Qian Chen PhD , Mengjuan Sun MD , Yanan Li PhD , Liping Huang PhD , Chang Zu PhD , Xiaoqin Kuang BD , Jianing Zhao BD , Mingyu Hao BD , Tingting Ma BD , Chunjiayu Li BD , Jiasheng Tu PhD , Chunmeng Sun PhD , Yunai Du PhD
Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic cancer vaccines, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and intratumoral administration of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for tumor treatment.
{"title":"Nano-vaccines combining customized in situ anti-PD-L1 depot for enhanced tumor immunotherapy","authors":"Qian Chen PhD , Mengjuan Sun MD , Yanan Li PhD , Liping Huang PhD , Chang Zu PhD , Xiaoqin Kuang BD , Jianing Zhao BD , Mingyu Hao BD , Tingting Ma BD , Chunjiayu Li BD , Jiasheng Tu PhD , Chunmeng Sun PhD , Yunai Du PhD","doi":"10.1016/j.nano.2023.102693","DOIUrl":"10.1016/j.nano.2023.102693","url":null,"abstract":"<div><p><span>Low response rate of immune checkpoint blockade (ICB) has limited its clinical application. A promising strategy to overcome this limitation is the use of therapeutic </span>cancer vaccines<span>, which aim to induce robust immune responses that synergize with ICB through immune enhancement and immune normalization strategies. Herein, we developed a combination immunotherapy<span><span> by combining nano-vaccines consisting of whole tumor cell lysates/CpG liposomes<span> (LCLs) with an anti-PD-L1 loaded lipid gel (aPD-L1@LG). The LCLs were fabricated using cationic liposomes, while the lipid gels (LGs) were prepared by using soybean </span></span>phosphatidylcholine<span><span> (SPC) and glycerol dioleate (GDO). Subcutaneous administration of LCLs successfully activated dendritic cells (DCs), and </span>intratumoral administration<span><span> of anti-PD-L1@LG ensured sustained ICB activity. These results demonstrated that this combination immunotherapy enhanced anti-tumor efficacy and prolonged the survival time in melanoma by activating systemic anti-tumor immune responses. These findings highlight the potential of this rational design as a promising strategy for </span>tumor treatment.</span></span></span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9983918","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}
PEGylated lipid nanoparticles (LNPs) are commonly used to deliver bioactive molecules, but the role of PEGylation in DNA-loaded LNP interactions at the cellular and subcellular levels remains poorly understood. In this study, we investigated the mechanism of action of DNA-loaded PEGylated LNPs using gene reporter technologies, dynamic light scattering (DLS), synchrotron small angle X-ray scattering (SAXS), and fluorescence confocal microscopy (FCS). We found that PEG has no significant impact on the size or nanostructure of DNA LNPs but reduces their zeta potential and interaction with anionic cell membranes. PEGylation increases the structural stability of LNPs and results in lower DNA unloading. FCS experiments revealed that PEGylated LNPs are internalized intact inside cells and largely shuttled to lysosomes, while unPEGylated LNPs undergo massive destabilization on the plasma membrane. These findings can inform the design, optimization, and validation of DNA-loaded LNPs for gene delivery and vaccine development.
{"title":"Investigating the mechanism of action of DNA-loaded PEGylated lipid nanoparticles","authors":"Luca Digiacomo PhD , Serena Renzi MSc , Erica Quagliarini PhD , Daniela Pozzi PhD , Heinz Amenitsch PhD , Gianmarco Ferri PhD , Luca Pesce PhD , Valentina De Lorenzi PhD , Giulia Matteoli MSc , Francesco Cardarelli PhD , Giulio Caracciolo (Prof.)","doi":"10.1016/j.nano.2023.102697","DOIUrl":"10.1016/j.nano.2023.102697","url":null,"abstract":"<div><p>PEGylated lipid nanoparticles (LNPs) are commonly used to deliver bioactive molecules, but the role of PEGylation in DNA-loaded LNP interactions at the cellular and subcellular levels remains poorly understood. In this study, we investigated the mechanism of action of DNA-loaded PEGylated LNPs using gene reporter technologies, dynamic light scattering (DLS), synchrotron small angle X-ray scattering (SAXS), and fluorescence confocal microscopy (FCS). We found that PEG has no significant impact on the size or nanostructure of DNA LNPs but reduces their zeta potential and interaction with anionic cell membranes. PEGylation increases the structural stability of LNPs and results in lower DNA unloading. FCS experiments revealed that PEGylated LNPs are internalized intact inside cells and largely shuttled to lysosomes, while unPEGylated LNPs undergo massive destabilization on the plasma membrane. These findings can inform the design, optimization, and validation of DNA-loaded LNPs for gene delivery and vaccine development.</p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1549963423000485/pdfft?md5=67c4c107222b327ba2036e697171b843&pid=1-s2.0-S1549963423000485-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937475","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 : 2023-09-01DOI: 10.1016/j.nano.2023.102698
Olegi N. Kukaliia MD , Sergei V. Ageev MSc , Andrey V. Petrov MSc , Olga V. Kirik PhD , Dmitrii E. Korzhevskii PhD , Anatolii A. Meshcheriakov PhD , Anastasia A. Jakovleva PhD , Liudmila S. Poliakova PhD , Tatiana A. Novikova PhD , Maria E. Kolpakova PhD , Timur D. Vlasov DSc , Oleg E. Molchanov DSc , Dmitriy N. Maistrenko DSc , Igor V. Murin DSc , Vladimir V. Sharoyko DSc , Konstantin N. Semenov DSc
The work aimed to investigate the biocompatibility and biological activity of the water-soluble fullerene adduct C60-Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of neuroprotectors. It has been suggested that a putative mechanism of the protective action of the C60-Arg adduct is associated with its antioxidant properties, the ability to penetrate the blood-brain barrier, and release nitrogen monoxide as a result of the catabolism of L-arginine residues, which promote vascular relaxation. The action of the C60-Arg adduct was compared with the action of such an antioxidant as Edaravone, which is approved in Japan for the treatment of ischemic and haemorrhagic strokes.
{"title":"C60 adduct with L-arginine as a promising nanomaterial for treating cerebral ischemic stroke","authors":"Olegi N. Kukaliia MD , Sergei V. Ageev MSc , Andrey V. Petrov MSc , Olga V. Kirik PhD , Dmitrii E. Korzhevskii PhD , Anatolii A. Meshcheriakov PhD , Anastasia A. Jakovleva PhD , Liudmila S. Poliakova PhD , Tatiana A. Novikova PhD , Maria E. Kolpakova PhD , Timur D. Vlasov DSc , Oleg E. Molchanov DSc , Dmitriy N. Maistrenko DSc , Igor V. Murin DSc , Vladimir V. Sharoyko DSc , Konstantin N. Semenov DSc","doi":"10.1016/j.nano.2023.102698","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102698","url":null,"abstract":"<div><p><span><span><span>The work aimed to investigate the biocompatibility and </span>biological activity of the water-soluble </span>fullerene adduct C</span><sub>60</sub><span><span>-Arg. It was found that the material is haemocompatible, is not cyto- and genotoxic, possesses pronounced antioxidant activity. Additionally, this paper outlines the direction of application of water-soluble fullerene adducts in the creation of </span>neuroprotectors. It has been suggested that a putative mechanism of the protective action of the C</span><sub>60</sub><span>-Arg adduct is associated with its antioxidant properties, the ability to penetrate the blood-brain barrier, and release nitrogen monoxide as a result of the catabolism of L-arginine residues, which promote vascular relaxation. The action of the C</span><sub>60</sub><span><span>-Arg adduct was compared with the action of such an antioxidant as Edaravone, which is approved in </span>Japan<span> for the treatment of ischemic and haemorrhagic strokes.</span></span></p></div>","PeriodicalId":19050,"journal":{"name":"Nanomedicine : nanotechnology, biology, and medicine","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92141685","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}