Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CD146 in gastric cancer
Nano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems....
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| Published in | International journal of nanomedicine Vol. 10; no. default; pp. 749 - 763 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
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New Zealand
Taylor & Francis Ltd
01.01.2015
Dove Press Dove Medical Press |
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| Abstract | Nano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.
Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core-shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW-SPION@dSiO2-YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW-SPION@dSiO2-YY146 to target tumor CD146.
800ZW-SPION@dSiO2-YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20-30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM(-1)·s(-1). Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW-SPION@dSiO2-YY146 more than the control group 800ZW-SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSiO2-YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection.
This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW-SPION@dSiO2-YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery. |
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| AbstractList | Purpose: Nano dense-silica (dSiO2) has many advantages such as adjustable core–shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems. Methods: Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core–shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core–shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW–SPION@dSiO2–YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW–SPION@dSiO2–YY146 to target tumor CD146. Results: 800ZW–SPION@dSiO2–YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20–30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM-1·s-1. Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW–SPION@dSiO2–YY146 more than the control group 800ZW–SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW–SPION@dSiO2–YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection. Conclusion: This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW–SPION@dSiO2–YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery. Nano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.Methods: Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core-shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW-SPION@dSiO2-YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW-SPION@dSiO2-YY146 to target tumor CD146.Results: 800ZW-SPION@dSiO2-YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20-30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM-1·s-1. Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW-SPION@dSiO2-YY146 more than the control group 800ZW-SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSiO2-YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection.Conclusion: This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW-SPION@dSiO2-YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery. PURPOSENano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.METHODSSuperparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core-shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW-SPION@dSiO2-YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW-SPION@dSiO2-YY146 to target tumor CD146.RESULTS800ZW-SPION@dSiO2-YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20-30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM(-1)·s(-1). Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW-SPION@dSiO2-YY146 more than the control group 800ZW-SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSiO2-YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection.CONCLUSIONThis is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW-SPION@dSiO2-YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery. Pu Wang,1,* Yazhuo Qu,2,* Chuan Li,3 Li Yin,2 Caifei Shen,1 Wei Chen,3 Shiming Yang,4 Xiuwu Bian,2 Dianchun Fang11Institute of Gastroenterology, 2Institute of Pathology, 3Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing, People's Republic of China; 4Department of Gastroenterology, Xinqiao Hospital, The Third Military Medical University, Chongqing, People's Republic of China*These authors contributed equally to this workPurpose: Nano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems.Methods: Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core-shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778nm/emission wavelength: 806nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW-SPION@dSiO2-YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW-SPION@dSiO2-YY146 to target tumor CD146.Results: 800ZW-SPION@dSiO2-YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20-30nm with 15nm SPION core and ~10nm SiO2 shell, and the final concentration was 1.7nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57mM-1·s-1. Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW-SPION@dSiO2-YY146 more than the control group 800ZW-SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSiO2-YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24hours postinjection.Conclusion: This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW-SPION@dSiO2-YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery.Keywords: SPION, nanotechnology, EMT, SPION@dSiO2, xenograft, gastric cancer Nano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the gastric tumor-specific targeting efficiency based on the development of various strategies is crucial for anti-cancer drug delivery systems. Superparamagnetic iron oxide nanoparticles (SPION) were coated with dSiO2 as core-shell nanoparticles, and labeled with near infra-red fluorescence (NIRF) dye 800ZW (excitation wavelength: 778 nm/emission wavelength: 806 nm) and anti-CD146 monoclonal antibody YY146 for magnetic resonance (MR)/NIRF imaging study in xenograft gastric cancer model. The morphology and the size of pre- and postlabeling SPION@dSiO2 core-shell nanoparticles were characterized using transmission electron microscopy. Iron content in SPION@dSiO2 nanoparticles was measured by inductively coupled plasma optical emission spectrometry. Fluorescence microscopy and fluorescence-activated cell sorter studies were carried out to confirm the binding specificity of YY146 and 800ZW-SPION@dSiO2-YY146 on MKN45 cells. In vivo and in vitro NIRF imaging, control (nanoparticles only) and blocking studies, and histology were executed on MKN45 tumor-bearing nude mice to estimate the affinity of 800ZW-SPION@dSiO2-YY146 to target tumor CD146. 800ZW-SPION@dSiO2-YY146 nanoparticles were uniformly spherical in shape and dispersed evenly in a cell culture medium. The diameter of the nanoparticle was 20-30 nm with 15 nm SPION core and ~10 nm SiO2 shell, and the final concentration was 1.7 nmol/mL. Transverse relaxivity of SPION@dSiO2 dispersed in water was measured to be 110.57 mM(-1)·s(-1). Fluorescence activated cell sorter analysis of the nanoparticles in MKN45 cells showed 14-fold binding of 800ZW-SPION@dSiO2-YY146 more than the control group 800ZW-SPION@dSiO2. Series of NIRF imaging post intravenous injection of 800ZW-SPION@dSiO2-YY146 demonstrated that the MKN45 xenograft tumor model could be clearly identified as early as a time point of 30 minutes postinjection. Quantitative analysis revealed that the tumor uptake peaked at 24 hours postinjection. This is the first successful study of functional nanoparticles for MR/NIRF imaging of cell surface glycoprotein CD146 in gastric cancer model. Our results suggest that 800ZW-SPION@dSiO2-YY146 nanoparticles will be applicable in tumor for image-guided therapy/surgery. |
| Author | Chen, Wei Bian, Xiuwu Qu, Yazhuo Yin, Li Li, Chuan Fang, Dianchun Yang, Shiming Wang, Pu Shen, Caifei |
| AuthorAffiliation | 2 Institute of Pathology, The Third Military Medical University, Chongqing, People’s Republic of China 3 Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing, People’s Republic of China 4 Department of Gastroenterology, Xinqiao Hospital, The Third Military Medical University, Chongqing, People’s Republic of China 1 Institute of Gastroenterology, The Third Military Medical University, Chongqing, People’s Republic of China |
| AuthorAffiliation_xml | – name: 2 Institute of Pathology, The Third Military Medical University, Chongqing, People’s Republic of China – name: 4 Department of Gastroenterology, Xinqiao Hospital, The Third Military Medical University, Chongqing, People’s Republic of China – name: 1 Institute of Gastroenterology, The Third Military Medical University, Chongqing, People’s Republic of China – name: 3 Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing, People’s Republic of China |
| Author_xml | – sequence: 1 givenname: Pu surname: Wang fullname: Wang, Pu organization: Institute of Gastroenterology, The Third Military Medical University, Chongqing, People's Republic of China – sequence: 2 givenname: Yazhuo surname: Qu fullname: Qu, Yazhuo organization: Institute of Pathology, The Third Military Medical University, Chongqing, People's Republic of China – sequence: 3 givenname: Chuan surname: Li fullname: Li, Chuan organization: Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing, People's Republic of China – sequence: 4 givenname: Li surname: Yin fullname: Yin, Li organization: Institute of Pathology, The Third Military Medical University, Chongqing, People's Republic of China – sequence: 5 givenname: Caifei surname: Shen fullname: Shen, Caifei organization: Institute of Gastroenterology, The Third Military Medical University, Chongqing, People's Republic of China – sequence: 6 givenname: Wei surname: Chen fullname: Chen, Wei organization: Department of Radiology, Southwest Hospital, The Third Military Medical University, Chongqing, People's Republic of China – sequence: 7 givenname: Shiming surname: Yang fullname: Yang, Shiming organization: Department of Gastroenterology, Xinqiao Hospital, The Third Military Medical University, Chongqing, People's Republic of China – sequence: 8 givenname: Xiuwu surname: Bian fullname: Bian, Xiuwu organization: Institute of Pathology, The Third Military Medical University, Chongqing, People's Republic of China – sequence: 9 givenname: Dianchun surname: Fang fullname: Fang, Dianchun organization: Institute of Gastroenterology, The Third Military Medical University, Chongqing, People's Republic of China |
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| Keywords | nanotechnology gastric cancer xenograft SPION EMT SPION@dSiO2 |
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| Snippet | Nano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior. Improving the... Purpose: Nano dense-silica (dSiO2) has many advantages such as adjustable core–shell structure, multiple drug delivery, and controllable release behavior.... PURPOSENano dense-silica (dSiO2) has many advantages such as adjustable core-shell structure, multiple drug delivery, and controllable release behavior.... Pu Wang,1,* Yazhuo Qu,2,* Chuan Li,3 Li Yin,2 Caifei Shen,1 Wei Chen,3 Shiming Yang,4 Xiuwu Bian,2 Dianchun Fang11Institute of Gastroenterology, 2Institute of... |
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| SubjectTerms | Angiogenesis Animals Antibodies, Monoclonal - chemistry Antibodies, Monoclonal - immunology Biocompatibility Biomedical materials Cancer therapies CD146 Antigen - immunology CD146 Antigen - metabolism Cell Line, Tumor Drug Delivery Systems EMT Esophagus Female Fluorescent Antibody Technique Gastric cancer Gastroenterology Humans Laboratory animals Life sciences Magnetic Resonance Imaging - methods Medical prognosis Metastasis Mice Mice, Nude Microscopy, Confocal Microscopy, Fluorescence - methods Nanoparticles Nanoparticles - chemistry Nanotechnology NMR Nuclear magnetic resonance Original Research Patients Silicon Dioxide - chemistry Skin cancer Spectrometry, Fluorescence - methods SPION SPION@dSiO2 Stomach Neoplasms - immunology Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Tumors xenograft |
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| Title | Bio-functionalized dense-silica nanoparticles for MR/NIRF imaging of CD146 in gastric cancer |
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