Recognition of Dextran–Superparamagnetic Iron Oxide Nanoparticle Conjugates (Feridex) via Macrophage Scavenger Receptor Charged Domains
Dextran-coated superparamagnetic iron oxide nanoparticles (dextran–SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIOs are rapidly removed by macrophages. We engineered embryonic...
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| Published in | Bioconjugate chemistry Vol. 23; no. 5; pp. 1003 - 1009 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
American Chemical Society
16.05.2012
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| Abstract | Dextran-coated superparamagnetic iron oxide nanoparticles (dextran–SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIOs are rapidly removed by macrophages. We engineered embryonic cells (HEK293T) to express major macrophage scavenger receptor (SR) subtypes including SR-AI, MARCO, and endothelial receptor collectin-12. These SRs possess a positively charged collagen-like (CL) domain and they promoted SPIO uptake, while the charge neutral lipoprotein receptor SR-BI did not. In silico modeling indicated a positive net charge on the CL domain and a net negative charge on the cysteine-rich (CR) domain of MARCO and SR-AI. In vitro experiments revealed that CR domain deletion in SR-AI boosted uptake of SPIO 3-fold, while deletion of MARCO’s CR domain abolished this uptake. These data suggest that future studies might productively focus on the validation and further exploration of SR charge fields in SPIO recognition. |
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| AbstractList | Dextran-coated superparamagnetic iron oxide nanoparticles (dextran–SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIOs are rapidly removed by macrophages. We engineered embryonic cells (HEK293T) to express major macrophage scavenger receptor (SR) subtypes including SR-AI, MARCO, and endothelial receptor collectin-12. These SRs possess a positively charged collagen-like (CL) domain and they promoted SPIO uptake, while the charge neutral lipoprotein receptor SR-BI did not. In silico modeling indicated a positive net charge on the CL domain and a net negative charge on the cysteine-rich (CR) domain of MARCO and SR-AI. In vitro experiments revealed that CR domain deletion in SR-AI boosted uptake of SPIO 3-fold, while deletion of MARCO’s CR domain abolished this uptake. These data suggest that future studies might productively focus on the validation and further exploration of SR charge fields in SPIO recognition. Dextran-coated superparamagnetic iron oxide nanoparticles (dextran-SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIOs are rapidly removed by macrophages. We engineered embryonic cells (HEK293T) to express major macrophage scavenger receptor (SR) subtypes including SR-AI, MARCO, and endothelial receptor collectin-12. These SRs possess a positively charged collagen-like (CL) domain and they promoted SPIO uptake, while the charge neutral lipoprotein receptor SR-BI did not. In silico modeling indicated a positive net charge on the CL domain and a net negative charge on the cysteine-rich (CR) domain of MARCO and SR-AI. In vitro experiments revealed that CR domain deletion in SR-AI boosted uptake of SPIO 3-fold, while deletion of MARCO's CR domain abolished this uptake. These data suggest that future studies might productively focus on the validation and further exploration of SR charge fields in SPIO recognition. [PUBLICATION ABSTRACT] Dextran-coated superparamagnetic iron oxide nanoparticles (dextran-SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so that small or diffuse lesions can be detected. However, systemically injected SPIO are rapidly removed by macrophages. We engineered embryonic cells (HEK293T) to express major macrophage scavenger receptor (SR) subtypes including SR-AI, MARCO, and endothelial receptor collectin-12. These SRs possess a positively charged collagen-like (CL) domain and they promoted SPIO uptake, while the charge neutral lipoprotein receptor SR-BI did not. In silico modeling indicated a positive net charge on the CL domain, and a net negative charge on the cysteine-rich (CR) domain of MARCO and SR-AI. In vitro experiments revealed that CR domain deletion in SR-AI boosted uptake of SPIO 3-fold, while deletion of MARCO's CR domain abolished this uptake. These data suggest that future studies might productively focus on the validation and further exploration of SR charge fields in SPIO recognition. |
| Author | Makale, Milan Wrasidlo, Wolf Karmali, Priya Prakash Ruoslahti, Erkki Merkulov, Sergei Sharikov, Yuriy Chao, Ying Tsigelny, Igor Simberg, Dmitri Kesari, Santosh |
| AuthorAffiliation | University of California San Diego San Diego Supercomputer Center Virogene LLC Sanford-Burnham Medical Research Institute at University of California Santa Barbara Moores Cancer Center, School of Medicine Sanford-Burnham Medical Research Institute Neuro-Oncology Program, Moores Cancer Center Department of Neurosciences |
| AuthorAffiliation_xml | – name: Virogene LLC – name: – name: Sanford-Burnham Medical Research Institute – name: Department of Neurosciences – name: San Diego Supercomputer Center – name: University of California San Diego – name: Sanford-Burnham Medical Research Institute at University of California Santa Barbara – name: Moores Cancer Center, School of Medicine – name: Neuro-Oncology Program, Moores Cancer Center – name: 2 Department of Neurosciences, University of California San Diego, La Jolla CA – name: 4 Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA – name: 1 Moores Cancer Center, School of Medicine, University of California San Diego, La Jolla CA – name: 3 Neuro-Oncology Program, Moores Cancer Center, UCSD – name: 5 San Diego Supercomputer Center, University of California San Diego, La Jolla CA – name: 6 Virogene LLC, Solon, OH – name: 7 Vascular Mapping Center, Sanford-Burnham Medical Research Institute at UCSB, University of California Santa Barbara, CA |
| Author_xml | – sequence: 1 givenname: Ying surname: Chao fullname: Chao, Ying – sequence: 2 givenname: Milan surname: Makale fullname: Makale, Milan – sequence: 3 givenname: Priya Prakash surname: Karmali fullname: Karmali, Priya Prakash – sequence: 4 givenname: Yuriy surname: Sharikov fullname: Sharikov, Yuriy – sequence: 5 givenname: Igor surname: Tsigelny fullname: Tsigelny, Igor – sequence: 6 givenname: Sergei surname: Merkulov fullname: Merkulov, Sergei – sequence: 7 givenname: Santosh surname: Kesari fullname: Kesari, Santosh – sequence: 8 givenname: Wolf surname: Wrasidlo fullname: Wrasidlo, Wolf – sequence: 9 givenname: Erkki surname: Ruoslahti fullname: Ruoslahti, Erkki – sequence: 10 givenname: Dmitri surname: Simberg fullname: Simberg, Dmitri email: dsimberg@ucsd.edu |
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| Snippet | Dextran-coated superparamagnetic iron oxide nanoparticles (dextran–SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so... Dextran-coated superparamagnetic iron oxide nanoparticles (dextran-SPIO conjugates) offer the attractive possibility of enhancing MRI imaging sensitivity so... |
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| StartPage | 1003 |
| SubjectTerms | Amino acids Biochemistry Cells Cloning, Molecular Collagen Collagen Type I - metabolism Contrast Media - metabolism Dextrans - metabolism HEK293 Cells Humans Macrophages - metabolism Magnetic Resonance Imaging Magnetite Nanoparticles Models, Molecular Nanoparticles Nanoparticles - metabolism Nanoparticles - ultrastructure NMR Nuclear magnetic resonance Protein Structure, Tertiary Receptors, Scavenger - chemistry Receptors, Scavenger - genetics Receptors, Scavenger - metabolism T cell receptors |
| Title | Recognition of Dextran–Superparamagnetic Iron Oxide Nanoparticle Conjugates (Feridex) via Macrophage Scavenger Receptor Charged Domains |
| URI | http://dx.doi.org/10.1021/bc200685a https://www.ncbi.nlm.nih.gov/pubmed/22515422 https://www.proquest.com/docview/1014152663 https://pubmed.ncbi.nlm.nih.gov/PMC3444675 |
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