| Superparamagnetic iron oxide nanotheranostics for targeted cancer cell imaging and pH-dependent intracellular drug release. | |
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MedLine Citation:
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PMID: 20845930 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Studies were conducted to develop antibody- and fluorescence-labeled superparamagnetic iron oxide nanoparticle (SPIO) nanotheranostics for magnetic resonance imaging (MRI) and fluorescence imaging of cancer cells and pH-dependent intracellular drug release. SPIO nanoparticles (10 nm) were coated with amphiphilic polymers and PEGylated. The antibody HuCC49ΔCH2 and fluorescent dye 5-FAM were conjugated to the PEG of iron oxide nanoparticles (IONPs). Anticancer drugs doxorubicin (Dox), azido-doxorubicin (Adox), MI-219, and 17-DMAG containing primary amine, azide, secondary amine, and tertiary amine, respectively, were encapsulated into IONPs. The encapsulation efficiency and drug release at various pHs were determined using LC-MS/MS. The cancer targeting and imaging were monitored using MRI and fluorescent microscopy in a colon cancer cell line (LS174T). The pH-dependent drug release, intracellular distribution, and cytotoxicity were evaluated using microscopy and MTS assay. The PEGylation of SPIO and conjugation with antibody and 5-FAM increased SPIO size from 18 to 44 nm. Fluorescent imaging, magnetic resonance imaging (MRI) and Prussian blue staining demonstrated that HuCC49ΔCH2-SPIO increased cancer cell targeting. HuCC49ΔCH2-SPIO nanotheranostics decreased the T(2) values in MRI of LS174T cells from 117.3 ± 1.8 ms to 55.5 ± 2.6 ms. The loading capacities of Dox, Adox, MI-219, and 17-DMAG were 3.16 ± 0.77%, 6.04 ± 0.61%, 2.22 ± 0.42%, and 0.09 ± 0.07%, respectively. Dox, MI-219 and 17-DMAG showed pH-dependent release while Adox did not. Fluorescent imaging demonstrated the accumulation of HuCC49ΔCH2-SPIO nanotheranostics in endosomes/lysosomes. The encapsulated Dox was released in acidic lysosomes and diffused into cytosol and nuclei. In contrast, the encapsulated Adox only showed limited release in endosomes/lysosomes. HuCC49ΔCH2-SPIO nanotheranostics target-delivered more Dox to LS174T cells than nonspecific IgG-SPIO and resulted in a lower IC(50) (1.44 μM vs 0.44 μM). The developed HuCC49ΔCH2-SPIO nanotheranostics provides an integrated platform for cancer cell imaging, targeted anticancer drug delivery and pH-dependently drug release. |
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Authors:
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Peng Zou; Yanke Yu; Y Andrew Wang; Yanqiang Zhong; Amanda Welton; Craig Galbán; Shaomeng Wang; Duxin Sun |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-29 |
Journal Detail:
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Title: Molecular pharmaceutics Volume: 7 ISSN: 1543-8392 ISO Abbreviation: Mol. Pharm. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-06 Completed Date: 2011-03-25 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 101197791 Medline TA: Mol Pharm Country: United States |
Other Details:
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Languages: eng Pagination: 1974-84 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies
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chemistry Antineoplastic Agents / pharmacology* Drug Delivery Systems Ferric Compounds / chemistry, diagnostic use* Fluorescent Dyes / chemistry Humans Hydrogen-Ion Concentration Magnetic Resonance Imaging Magnetics* Microscopy, Fluorescence Nanostructures / chemistry* Neoplasms / diagnosis*, drug therapy Particle Size Polyethylene Glycols / chemistry Surface Properties Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA120023/CA/NCI NIH HHS; R01 CA120023-05/CA/NCI NIH HHS; R21 CA143474/CA/NCI NIH HHS; R21 CA143474-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Antineoplastic Agents; 0/Ferric Compounds; 0/Fluorescent Dyes; 0/Polyethylene Glycols; 1309-37-1/ferric oxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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