Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102633
Ariane Mwema M BBMC , Pauline Bottemanne PhD , Adrien Paquot M FARM , Bernard Ucakar Bachelor , Kevin Vanvarenberg Bachelor , Mireille Alhouayek PhD , Giulio G. Muccioli PhD , Anne des Rieux PhD
Here, prostaglandin D2-glycerol ester (PGD2-G) was selected to target neuroinflammation. As PGD2-G is reported to have a short plasmatic half-life, we propose to use lipid nanocapsules (LNC) as vehicle to safely transport PGD2-G to the central nervous system (CNS). PGD2-G-loaded LNC (PGD2-G-LNC) reduced pro-inflammatory cytokine expression in activated microglial cells, even so after crossing a primary olfactory cell monolayer. A single nasal administration of PGD2-G-LNC in lipopolysaccharide (LPS)-treated mice reduced pro-inflammatory cytokine expression in the olfactory bulb. Coating LNC's surface with a cell-penetrating peptide, transactivator of transcription (TAT), increased its accumulation in the brain. Although TAT-coated PGD2-G-LNC modestly exerted its anti-inflammatory effect in a mouse model of multiple sclerosis similar to free PGD2-G after nasal administration, TAT-coated LNC surprisingly reduced the expression of pro-inflammatory chemokines in the CNS. These data propose LNC as an interesting drug delivery tool and TAT-coated PGD2-G-LNC remains a good candidate, in need of further work.
{"title":"Lipid nanocapsules for the nose-to-brain delivery of the anti-inflammatory bioactive lipid PGD2-G","authors":"Ariane Mwema M BBMC , Pauline Bottemanne PhD , Adrien Paquot M FARM , Bernard Ucakar Bachelor , Kevin Vanvarenberg Bachelor , Mireille Alhouayek PhD , Giulio G. Muccioli PhD , Anne des Rieux PhD","doi":"10.1016/j.nano.2022.102633","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102633","url":null,"abstract":"<div><p>Here, prostaglandin D<sub>2</sub>-glycerol ester (PGD<sub>2</sub>-G) was selected to target neuroinflammation. As PGD<sub>2</sub>-G is reported to have a short plasmatic half-life, we propose to use lipid nanocapsules (LNC) as vehicle to safely transport PGD<sub>2</sub>-G to the central nervous system (CNS). PGD<sub>2</sub>-G-loaded LNC (PGD<sub>2</sub>-G-LNC) reduced pro-inflammatory cytokine expression in activated microglial cells, even so after crossing a primary olfactory cell monolayer. A single nasal administration of PGD<sub>2</sub>-G-LNC in lipopolysaccharide (LPS)-treated mice reduced pro-inflammatory cytokine expression in the olfactory bulb. Coating LNC's surface with a cell-penetrating peptide, transactivator of transcription (TAT), increased its accumulation in the brain. Although TAT-coated PGD<sub>2</sub>-G-LNC modestly exerted its anti-inflammatory effect in a mouse model of multiple sclerosis similar to free PGD<sub>2</sub>-G after nasal administration, TAT-coated LNC surprisingly reduced the expression of pro-inflammatory chemokines in the CNS. These data propose LNC as an interesting drug delivery tool and TAT-coated PGD<sub>2</sub>-G-LNC remains a good candidate, in need of further work.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3457442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chemoradiotherapy with controlled-release nanocarriers such as sono-sensitive nanodroplets (NDs) can enhance the anticancer activity of chemotherapy medicines and reduces normal tissue side effects. In this study, folic acid-functionalized methotrexate-loaded perfluorohexane NDs with alginate shell (FA-MTX/PFH@alginate NDs) were synthesized, characterized, and their potential for ultrasound-guided chemoradiotherapy of breast cancer was investigated in vitro and in vivo. The cancer cell (4T1) viabilities and surviving fractions after NDs and ultrasound treatments were significantly decreased. However, this reduction was much more significant for ultrasound in combination with X-ray irradiation. The in vitro and in vivo results confirmed that MTX-loaded NDs are highly biocompatible and they have no significant hemolytic activity and organ toxicity. Furthermore, the in vivo results indicated that the FA-MTX/PFH@alginate NDs were accumulated selectively in the tumor region. In conclusion, FA-functionalized MTX/PFH@alginate NDs have a great theranostic performance for ultrasound-controlled drug delivery in combination with radiotherapy of breast cancer.
{"title":"Ultrasound-guided chemoradiotherapy of breast cancer using smart methotrexate-loaded perfluorohexane nanodroplets","authors":"Roghayeh Kamran Samani PhD , Fatemeh Maghsoudinia PhD , Fatemeh Mehradnia PhD , Seyed Hossein Hejazi PhD , Mohsen Saeb PhD , Tayebe Sobhani MSc , Zohreh Farahbakhsh MSc , Masoud A. Mehrgardi PhD , Mohamad Bagher Tavakoli PhD","doi":"10.1016/j.nano.2022.102643","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102643","url":null,"abstract":"<div><p><span><span>Chemoradiotherapy with controlled-release </span>nanocarriers<span><span> such as sono-sensitive nanodroplets (NDs) can enhance the anticancer activity of chemotherapy medicines and reduces normal tissue side effects. In this study, folic acid-functionalized methotrexate-loaded </span>perfluorohexane<span> NDs with alginate shell (FA-MTX/PFH@alginate NDs) were synthesized, characterized, and their potential for ultrasound-guided chemoradiotherapy of breast cancer was investigated </span></span></span><em>in vitro</em> and <em>in vivo</em><span><span>. The cancer cell (4T1) viabilities and surviving fractions after NDs and ultrasound </span>treatments were significantly decreased. However, this reduction was much more significant for ultrasound in combination with X-ray irradiation. The </span><em>in vitro</em> and <em>in vivo</em><span><span> results confirmed that MTX-loaded NDs are highly biocompatible and they have no significant hemolytic activity and </span>organ toxicity. Furthermore, the </span><em>in vivo</em><span> results indicated that the FA-MTX/PFH@alginate NDs were accumulated selectively in the tumor region. In conclusion, FA-functionalized MTX/PFH@alginate NDs have a great theranostic performance for ultrasound-controlled drug delivery in combination with radiotherapy of breast cancer.</span></p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3457443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2023.102657
Joanna Depciuch PhD , Paweł Jakubczyk Prof. , Wiesław Paja PhD , Krzysztof Pancerz PhD , Agnieszka Wosiak Prof. , Monika Kula-Maximenko PhD , İlhan Yaylım Prof. , Güldal İnal Gültekin Prof. , Nevzat Tarhan Prof. , Mehmet Tolgahan Hakan PhD , Dilara Sönmez M.Sc , Devrim Sarıbal Prof. , Soykan Arıkan Prof. , Zozan Guleken Prof.
Colorectal cancer is the second most common cause of cancer-related deaths worldwide. To follow up on the progression of the disease, tumor markers are commonly used. Here, we report serum analysis based on Raman spectroscopy to provide a rapid cancer diagnosis with tumor markers and two new cell adhesion molecules measured using the ELİSA method. Raman spectra showed higher Raman intensities at 1447 cm−1 1560 cm−1, 1665 cm-1, and 1769 cm−1, which originated from CH2 proteins and lipids, amide II and amide I, and CO lipids vibrations. Furthermore, the correlation test showed, that only the CEA colon cancer marker correlated with the Raman spectra. Importantly, machine learning methods showed, that the accuracy of the Raman method in the detection of colon cancer was around 95 %. Obtained results suggest, that Raman shifts at 1302 cm−1 and 1306 cm−1 can be used as spectroscopy markers of colon cancer.
{"title":"Correlation between human colon cancer specific antigens and Raman spectra. Attempting to use Raman spectroscopy in the determination of tumor markers for colon cancer","authors":"Joanna Depciuch PhD , Paweł Jakubczyk Prof. , Wiesław Paja PhD , Krzysztof Pancerz PhD , Agnieszka Wosiak Prof. , Monika Kula-Maximenko PhD , İlhan Yaylım Prof. , Güldal İnal Gültekin Prof. , Nevzat Tarhan Prof. , Mehmet Tolgahan Hakan PhD , Dilara Sönmez M.Sc , Devrim Sarıbal Prof. , Soykan Arıkan Prof. , Zozan Guleken Prof.","doi":"10.1016/j.nano.2023.102657","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102657","url":null,"abstract":"<div><p>Colorectal cancer is the second most common cause of cancer-related deaths worldwide. To follow up on the progression of the disease, tumor markers are commonly used. Here, we report serum analysis based on Raman spectroscopy to provide a rapid cancer diagnosis with tumor markers and two new cell adhesion molecules measured using the ELİSA method. Raman spectra showed higher Raman intensities at 1447 cm<sup>−1</sup> 1560 cm<sup>−1</sup>, 1665 cm<sup>-1,</sup> and 1769 cm<sup>−1</sup>, which originated from CH<sub>2</sub> proteins and lipids, amide II and amide I, and C<img>O lipids vibrations. Furthermore, the correlation test showed, that only the CEA colon cancer marker correlated with the Raman spectra. Importantly, machine learning methods showed, that the accuracy of the Raman method in the detection of colon cancer was around 95 %. Obtained results suggest, that Raman shifts at 1302 cm<sup>−1</sup> and 1306 cm<sup>−1</sup> can be used as spectroscopy markers of colon cancer.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"2377483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102646
Wenmin Yuan Ph.D. , Kelsey Ernst PharmD , Rui Kuai Ph.D. , Emily E. Morin Ph.D. , Minzhi Yu Ph.D. , Denis O. Sviridov Ph.D. , Jie Tang Ph.D. , Ling Mei Ph.D. , Dan Li Ph.D. , Rose Ackermann MS , Alan T. Remaley M.D., Ph.D. , Anna Schwendeman Ph.D.
Synthetic high-density lipoproteins nanomedicine (sHDL) composed of apolipoprotein A-I (ApoA-I) mimetic peptides and lipids have shown very promising results for the treatment of various cardiovascular diseases. Numerous efforts have also been made to design different ApoA-I mimetic peptides to improve the potency of sHDL, especially the efficiency of reverse cholesterol transport. However, the way in which ApoA-I mimetic peptides affect the properties of sHDL, including stability, cholesterol efflux, cholesterol esterification, elimination in vivo, and the relationship of these properties, is still poorly understood. Revealing the effect of these factors on the potency of sHDL is important for the design of better ApoA-I mimetic peptides. In this study, three widely used ApoA-I mimetic peptides with different sequences, lengths, LCAT activation and lipid binding affinities were used for the preparation of sHDL and were evaluated in terms of physical/chemical properties, cholesterol efflux, cholesterol esterification, remodeling, and pharmacokinetics/pharmacodynamics. Our results showed that ApoA-I mimetic peptides with the highest cholesterol efflux and cholesterol esterification in vitro did not exhibit the highest cholesterol mobilization in vivo. Further analysis indicated that other factors, such as pharmacokinetics and remodeling of sHDL, need to be considered in order to predict the efficiency of cholesterol mobilization in vivo. Thus, our study highlights the importance of using the overall performance, rather than in vitro results alone, as the blueprint for the design and optimization of ApoA-I mimetic peptides.
{"title":"Systematic evaluation of the effect of different apolipoprotein A-I mimetic peptides on the performance of synthetic high-density lipoproteins in vitro and in vivo","authors":"Wenmin Yuan Ph.D. , Kelsey Ernst PharmD , Rui Kuai Ph.D. , Emily E. Morin Ph.D. , Minzhi Yu Ph.D. , Denis O. Sviridov Ph.D. , Jie Tang Ph.D. , Ling Mei Ph.D. , Dan Li Ph.D. , Rose Ackermann MS , Alan T. Remaley M.D., Ph.D. , Anna Schwendeman Ph.D.","doi":"10.1016/j.nano.2022.102646","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102646","url":null,"abstract":"<div><p><span><span>Synthetic high-density lipoproteins nanomedicine<span> (sHDL) composed of apolipoprotein A-I (ApoA-I) </span></span>mimetic peptides<span><span> and lipids have shown very promising results for the </span>treatment<span> of various cardiovascular diseases. Numerous efforts have also been made to design different ApoA-I mimetic peptides to improve the potency of sHDL, especially the efficiency of reverse cholesterol transport<span>. However, the way in which ApoA-I mimetic peptides affect the properties of sHDL, including stability, cholesterol efflux, cholesterol esterification, elimination </span></span></span></span><em>in vivo</em><span><span>, and the relationship of these properties, is still poorly understood. Revealing the effect of these factors on the potency of sHDL is important for the design of better ApoA-I mimetic peptides. In this study, three widely used ApoA-I mimetic peptides with different sequences, lengths, LCAT activation and lipid </span>binding affinities were used for the preparation of sHDL and were evaluated in terms of physical/chemical properties, cholesterol efflux, cholesterol esterification, remodeling, and pharmacokinetics/pharmacodynamics. Our results showed that ApoA-I mimetic peptides with the highest cholesterol efflux and cholesterol esterification </span><em>in vitro</em> did not exhibit the highest cholesterol mobilization <em>in vivo</em><span>. Further analysis indicated that other factors, such as pharmacokinetics and remodeling of sHDL, need to be considered in order to predict the efficiency of cholesterol mobilization </span><em>in vivo</em>. Thus, our study highlights the importance of using the overall performance, rather than <em>in vitro</em> results alone, as the blueprint for the design and optimization of ApoA-I mimetic peptides.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3210035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102640
Jun Liu MM , Xiaochun Chen BS , Lei Xu MM , Fan Tu BS , Xiaohong Rui BS , Lizhu Zhang MM , Zhihan Yan BS , Yun Liu MM , Renjing Hu BS
Objective
To investigate the efficacy and safety of neutrophil membrane-coated nanoparticles mediated KLA peptides (KLAKLAKKLAKLAK) and gentamicin in the targeted therapy of anti-microbial resistant Klebsiella pneumoniae (K. pneumonia) lung infection.
Methods
The characteristics of KLA-neutrophils nanoparticles (NNPs) are identified via dynamic light scattering (DLS), transmission electron microscope (TEM), SDS-PAGE, Western blot, quantitative flow cytometry (QFCM) and confocal microscopy. The safety of KLA-NNPs both in vitro and in vivo is evaluated by hemolysis test, platelet α granule membrane protein concentration, protein adsorption capacity, in vitro macrophage phagocytosis, weight change, liver function indicators, blood biochemical indicators, and pathological changes of vital organs in mice. The efficacy of KLA-NNPs is determined by time-kill assay, fluorescent label test, intracellular bacterial content, caspase-1 activity, survival rate, and HE staining both in vitro and in vivo.
Results
The prepared KLA-NNPs have a typical “core-shell” structure, uniform nanometer size, and retain the membrane proteins on the neutrophil membrane that achieve functional effects. In vitro safety analysis showed that KLA-NNPs have good blood compatibility and can inhibit macrophage phagocytosis in vitro. KLA-NNPs can effectively release KLA and significantly reduce intracellular bacteria and caspase-1 activity. In vivo safety analysis and efficacy analysis revealed that KLA-NNPs have good biocompatibility and could effectively improve the survival rate of mice.
Conclusion
The prepared KLA-NNPs have good nano-medicine chemical and physical properties and safety. It can evade immune system clearance, achieve high-efficiency targeted aggregation and drug delivery to bacterial infection sites, and effectively inhibit the development of pneumonia induced by drug-resistant K. pneumonia.
{"title":"Neutrophil membrane-coated nanoparticles exhibit increased antimicrobial activities in an anti-microbial resistant K. pneumonia infection model","authors":"Jun Liu MM , Xiaochun Chen BS , Lei Xu MM , Fan Tu BS , Xiaohong Rui BS , Lizhu Zhang MM , Zhihan Yan BS , Yun Liu MM , Renjing Hu BS","doi":"10.1016/j.nano.2022.102640","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102640","url":null,"abstract":"<div><h3>Objective</h3><p><span>To investigate the efficacy and safety of neutrophil<span><span><span> membrane-coated nanoparticles mediated KLA peptides (KLAKLAKKLAKLAK) and </span>gentamicin in the </span>targeted therapy of anti-microbial resistant </span></span><span><em>Klebsiella </em><em>pneumoniae</em></span> (<em>K. pneumonia</em>) lung infection.</p></div><div><h3>Methods</h3><p>The characteristics of KLA-neutrophils nanoparticles (NNPs) are identified <em>via</em><span><span><span> dynamic light scattering (DLS), transmission </span>electron microscope<span> (TEM), SDS-PAGE, Western blot, quantitative flow cytometry (QFCM) and </span></span>confocal microscopy. The safety of KLA-NNPs both </span><em>in vitro</em> and <em>in vivo</em><span><span><span> is evaluated by hemolysis test, platelet α granule </span>membrane protein concentration, protein </span>adsorption capacity, </span><em>in vitro</em><span> macrophage phagocytosis<span><span>, weight change<span>, liver function indicators, blood biochemical indicators, and pathological changes of vital organs in mice. The efficacy of KLA-NNPs is determined by time-kill assay, </span></span>fluorescent label test, intracellular bacterial content, caspase-1 activity, survival rate, and HE staining both </span></span><em>in vitro</em> and <em>in vivo</em>.</p></div><div><h3>Results</h3><p><span>The prepared KLA-NNPs have a typical “core-shell” structure, uniform nanometer size, and retain the membrane proteins on the neutrophil membrane that achieve functional effects. </span><em>In vitro</em> safety analysis showed that KLA-NNPs have good blood compatibility and can inhibit macrophage phagocytosis <em>in vitro</em><span>. KLA-NNPs can effectively release KLA and significantly reduce intracellular bacteria and caspase-1 activity. </span><em>In vivo</em><span> safety analysis and efficacy analysis revealed that KLA-NNPs have good biocompatibility and could effectively improve the survival rate of mice.</span></p></div><div><h3>Conclusion</h3><p><span>The prepared KLA-NNPs have good nano-medicine chemical and physical properties and safety. It can evade immune system clearance, achieve high-efficiency targeted aggregation and drug delivery to bacterial infection sites, and effectively inhibit the development of pneumonia induced by drug-resistant </span><em>K. pneumonia</em>.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3457445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102641
Qiaoling Zhu MD , Yajie Wang MD , Ying Huang MD , Yixuan Zi MD , Simin Yan PhD , Xianbiao Shi PhD , Jun Cai MD , Haixia Zhang MD , Jianfeng Sang PhD , Wenli Zhang PhD , Weihong Ge MD
Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion in vitro. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis in vivo. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.
{"title":"Bioinspired low-density lipoprotein co-delivery system for targeting and synergistic cancer therapy","authors":"Qiaoling Zhu MD , Yajie Wang MD , Ying Huang MD , Yixuan Zi MD , Simin Yan PhD , Xianbiao Shi PhD , Jun Cai MD , Haixia Zhang MD , Jianfeng Sang PhD , Wenli Zhang PhD , Weihong Ge MD","doi":"10.1016/j.nano.2022.102641","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102641","url":null,"abstract":"<div><p>Epithelial-mesenchymal transition (EMT) is the culprit of tumor invasion and metastasis. As a critical transcription factor that induces EMT, snail is of great importance in tumor progression, and knocking down its expression by small interfering RNA (siRNA) may inhibit tumor metastasis. Herein, we developed a core-shelled bioinspired low-density lipoprotein (bio-LDL) in which snail siRNA-loaded calcium phosphate nanoparticles were wrapped as the core and doxorubicin was embedded in the outer phospholipids modified with a synthetic peptide of apoB100 targeting LDL receptor-abundant tumor cells. Bio-LDL exhibited pH-responsive release, lysosomal escape ability, enhanced cytotoxicity and apoptotic induction. Bio-LDL could significantly inhibit the expression of snail and regulate EMT-related proteins to reduce tumor migration and invasion <em>in vitro</em>. Bio-LDL also displayed favorable tumor targeting and synergistic inhibition of tumor growth and metastasis <em>in vivo</em>. Therefore, the multifunctional bio-LDL will be a promising co-delivery vector and holds potential value for clinical translation.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"1567235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2023.102650
Sarah Schraven MSc , Stefanie Rosenhain PhD , Ramona Brueck , Tim Marvin Wiechmann MSc , Robert Pola PhD , Tomáš Etrych PhD , Wiltrud Lederle DSc , Twan Lammers PhD , Felix Gremse PhD , Fabian Kiessling MD
Biodistribution analyses of nanocarriers are often performed with optical imaging. Though dye tags can interact with transporters, e.g., organic anion transporting polypeptides (OATPs), their influence on biodistribution was hardly studied. Therefore, this study compared tumor cell uptake and biodistribution (in A431 tumor-bearing mice) of four near-infrared fluorescent dyes (AF750, IRDye750, Cy7, DY-750) and dye-labeled poly(N-(2-hydroxypropyl)methacrylamide)-based nanocarriers (dye-pHPMAs). Tumor cell uptake of hydrophobic dyes (Cy7, DY-750) was higher than that of hydrophilic dyes (AF750, IRDye750), and was actively mediated but not related to OATPs. Free dyes' elimination depended on their hydrophobicity, and tumor uptake correlated with blood circulation times. Dye-pHPMAs circulated longer and accumulated stronger in tumors than free dyes. Dye labeling significantly influenced nanocarriers' tumor accumulation and biodistribution. Therefore, low-interference dyes and further exploration of dye tags are required to achieve the most unbiased results possible. In our assessment, AF750 and IRDye750 best qualified for labeling hydrophilic nanocarriers.
{"title":"Dye labeling for optical imaging biases drug carriers' biodistribution and tumor uptake","authors":"Sarah Schraven MSc , Stefanie Rosenhain PhD , Ramona Brueck , Tim Marvin Wiechmann MSc , Robert Pola PhD , Tomáš Etrych PhD , Wiltrud Lederle DSc , Twan Lammers PhD , Felix Gremse PhD , Fabian Kiessling MD","doi":"10.1016/j.nano.2023.102650","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102650","url":null,"abstract":"<div><p><span><span>Biodistribution analyses of </span>nanocarriers<span><span> are often performed with optical imaging. Though dye tags can interact with transporters, e.g., organic anion transporting </span>polypeptides<span> (OATPs), their influence on biodistribution was hardly studied. Therefore, this study compared tumor cell uptake and biodistribution (in A431 tumor-bearing mice) of four near-infrared fluorescent dyes (AF750, IRDye750, Cy7, DY-750) and dye-labeled poly(</span></span></span><em>N</em><span><span>-(2-hydroxypropyl)methacrylamide)-based nanocarriers (dye-pHPMAs). Tumor cell uptake of hydrophobic dyes (Cy7, DY-750) was higher than that of hydrophilic dyes (AF750, IRDye750), and was actively mediated but not related to OATPs. Free dyes' elimination depended on their </span>hydrophobicity<span>, and tumor uptake correlated with blood circulation times. Dye-pHPMAs circulated longer and accumulated stronger in tumors than free dyes. Dye labeling significantly influenced nanocarriers' tumor accumulation and biodistribution. Therefore, low-interference dyes and further exploration of dye tags are required to achieve the most unbiased results possible. In our assessment, AF750 and IRDye750 best qualified for labeling hydrophilic nanocarriers.</span></span></p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"2891282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2023.102656
Astrid Hyldbakk M.Sc. , Karianne Giller Fleten PhD , Sofie Snipstad PhD , Andreas K.O. Åslund PhD , Catharina de Lange Davies PhD , Kjersti Flatmark MD, PhD , Yrr Mørch PhD
Colorectal and ovarian cancers frequently develop peritoneal metastases with few treatment options. Intraperitoneal chemotherapy has shown promising therapeutic effects, but is limited by rapid drug clearance and systemic toxicity. We therefore encapsulated the cabazitaxel taxane in poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs), designed to improve intraperitoneal delivery. Toxicity of free and encapsulated cabazitaxel was investigated in rats by monitoring clinical signs, organ weight and blood hematological and biochemical parameters. Pharmacokinetics, biodistribution and treatment response were evaluated in mice. Biodistribution was investigated by measuring both cabazitaxel and the 2-ethylbutanol NP degradation product. Drug encapsulation was shown to increase intraperitoneal drug retention, leading to prolonged intraperitoneal drug residence time and higher drug concentrations in peritoneal tumors. As a result, encapsulation of cabazitaxel improved the treatment response in two in vivo models bearing intraperitoneal tumors. Together, these observations indicate a strong therapeutic potential of NP-based cabazitaxel encapsulation as a novel treatment for peritoneal metastases.
{"title":"Intraperitoneal administration of cabazitaxel-loaded nanoparticles in peritoneal metastasis models","authors":"Astrid Hyldbakk M.Sc. , Karianne Giller Fleten PhD , Sofie Snipstad PhD , Andreas K.O. Åslund PhD , Catharina de Lange Davies PhD , Kjersti Flatmark MD, PhD , Yrr Mørch PhD","doi":"10.1016/j.nano.2023.102656","DOIUrl":"https://doi.org/10.1016/j.nano.2023.102656","url":null,"abstract":"<div><p>Colorectal and ovarian cancers frequently develop peritoneal metastases with few treatment options. Intraperitoneal chemotherapy has shown promising therapeutic effects, but is limited by rapid drug clearance and systemic toxicity. We therefore encapsulated the cabazitaxel taxane in poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs), designed to improve intraperitoneal delivery. Toxicity of free and encapsulated cabazitaxel was investigated in rats by monitoring clinical signs, organ weight and blood hematological and biochemical parameters. Pharmacokinetics, biodistribution and treatment response were evaluated in mice. Biodistribution was investigated by measuring both cabazitaxel and the 2-ethylbutanol NP degradation product. Drug encapsulation was shown to increase intraperitoneal drug retention, leading to prolonged intraperitoneal drug residence time and higher drug concentrations in peritoneal tumors. As a result, encapsulation of cabazitaxel improved the treatment response in two <em>in vivo</em> models bearing intraperitoneal tumors. Together, these observations indicate a strong therapeutic potential of NP-based cabazitaxel encapsulation as a novel treatment for peritoneal metastases.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"2891287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102642
Long Zhang PhD , Nicolas Burns BS , Zhouxiang Ji PhD , Steven Sun PhD , Susan L. Deutscher PhD , William E. Carson III MD , Peixuan Guo Ph.D. (Director of Center for Nanobiotechnology and Nanomedicine)
Detection of cancer in its early stage is a challenging task for oncologists. Inflammatory breast cancer has symptoms that are similar to mastitis and can be mistaken for microbial infection. Currently, the differential diagnosis between mastitis and Inflammatory breast cancer via nipple aspirate fluid (NAF) is difficult. Here, we report a label-free and amplification-free detection platform using an engineered nanopore of the phi29 DNA-packaging motor with biomarker Galectin3 (GAL3), Thomsen-Friedenreich (TF) binding peptide as the probe fused at its C-terminus. The binding of the biomarker in NAF samples from breast cancer patients to the probe results in the connector's conformational change with a current blockage of 32 %. Utilization of dwell time, blockage ratio, and peak signature enable us to detect basal levels of biomarkers from patient NAF samples at the single-molecule level. This platform will allow for breast cancers to be resolved at an early stage with accuracy and thoroughness.
{"title":"Nipple fluid for breast cancer diagnosis using the nanopore of Phi29 DNA-packaging motor","authors":"Long Zhang PhD , Nicolas Burns BS , Zhouxiang Ji PhD , Steven Sun PhD , Susan L. Deutscher PhD , William E. Carson III MD , Peixuan Guo Ph.D. (Director of Center for Nanobiotechnology and Nanomedicine)","doi":"10.1016/j.nano.2022.102642","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102642","url":null,"abstract":"<div><p>Detection of cancer in its early stage is a challenging task for oncologists. Inflammatory breast cancer has symptoms that are similar to mastitis and can be mistaken for microbial infection. Currently, the differential diagnosis between mastitis and Inflammatory breast cancer via nipple aspirate fluid (NAF) is difficult. Here, we report a label-free and amplification-free detection platform using an engineered nanopore of the phi29 DNA-packaging motor with biomarker Galectin3 (GAL3), Thomsen-Friedenreich (TF) binding peptide as the probe fused at its C-terminus. The binding of the biomarker in NAF samples from breast cancer patients to the probe results in the connector's conformational change with a current blockage of 32 %. Utilization of dwell time, blockage ratio, and peak signature enable us to detect basal levels of biomarkers from patient NAF samples at the single-molecule level. This platform will allow for breast cancers to be resolved at an early stage with accuracy and thoroughness.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10035634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"2891285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-02-01DOI: 10.1016/j.nano.2022.102634
Xiaofei Xin PhD , Yong Zhou M.S. , Jingjing Li M.S. , Kai Zhang PhD , Chao Qin PhD , Lifang Yin PhD
The interplay of liposome-protein corona hinders the clinical application of liposomes due to active macrophage sequestration and rapid plasma clearance. Here we showed that, CXCL10 as a therapeutic protein was coronated the thermosensitive liposomes to form stealth-like nanocarriers (CXCL10/TSLs). Decoration of the corona layer of CXCL10/TSLs by hyaluronic acid conjugated oridonin (ORD/CXCL10/TSLs), overcame the “fluid barrier” built by biological proteins, drastically reduced capture by leukocytes in whole blood, allowed the specific targeting of tumor sites. Multifunctional medicine ORD/CXCL10/TSLs with hyperthermia drove the sustained cytokine-CXCL10 inflammatory loop to switch macrophage phenotype to M1-like, expand tumor-infiltrating natural killer cells and induce intratumoral levels of interferon-γ. Oridonin synergized with CXCL10 during ORD/CXCL10/TSLs treatment, downregulated PI3K/AKT and Raf/MEK signaling for M1-like polarization and migration inhibition. Furthermore, ORD/CXCL10/TSLs potently synergized with anti-PD-L1 antibody in mice bearing metastatic melanoma, induced sustained immunological memory and controlled metastatic spread.
{"title":"CXCL10-coronated thermosensitive “stealth” liposomes for sequential chemoimmunotherapy in melanoma","authors":"Xiaofei Xin PhD , Yong Zhou M.S. , Jingjing Li M.S. , Kai Zhang PhD , Chao Qin PhD , Lifang Yin PhD","doi":"10.1016/j.nano.2022.102634","DOIUrl":"https://doi.org/10.1016/j.nano.2022.102634","url":null,"abstract":"<div><p><span><span><span><span><span>The interplay<span> of liposome-protein corona hinders the clinical application of liposomes due to active macrophage sequestration and rapid plasma clearance. Here we showed that, </span></span>CXCL10 as a </span>therapeutic protein was coronated the thermosensitive liposomes to form stealth-like </span>nanocarriers<span> (CXCL10/TSLs). Decoration of the corona layer of CXCL10/TSLs by hyaluronic acid conjugated </span></span>oridonin<span><span><span><span> (ORD/CXCL10/TSLs), overcame the “fluid barrier” built by biological proteins, drastically reduced capture by leukocytes in whole blood, allowed the specific targeting of tumor sites. Multifunctional medicine ORD/CXCL10/TSLs with hyperthermia drove the sustained cytokine-CXCL10 inflammatory loop to switch macrophage phenotype to M1-like, expand tumor-infiltrating </span>natural killer cells and induce intratumoral levels of interferon-γ. Oridonin synergized with CXCL10 during ORD/CXCL10/TSLs </span>treatment, downregulated PI3K/AKT and Raf/MEK signaling for M1-like polarization and migration inhibition. Furthermore, ORD/CXCL10/TSLs potently synergized with anti-PD-L1 antibody in mice bearing </span>metastatic melanoma, induced sustained </span></span>immunological memory and controlled metastatic spread.</p></div>","PeriodicalId":396,"journal":{"name":"Nanomedicine: Nanotechnology, Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3341946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}