Synthesis, Characterization, and Biological Evaluation of Integrin αvβ3-Targeted PAMAM Dendrimers
| العنوان: | Synthesis, Characterization, and Biological Evaluation of Integrin αvβ3-Targeted PAMAM Dendrimers |
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| المؤلفون: | Peter Eck, Peter L. Choyke, Celeste A. S. Regino, Marcelino Bernardo, Karen J. Wong, Diane E. Milenic, C. A. Boswell, Martin W. Brechbiel |
| المصدر: | Molecular Pharmaceutics. 5:527-539 |
| بيانات النشر: | American Chemical Society (ACS), 2008. |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Dendrimers, Gadolinium, Mice, Nude, Pharmaceutical Science, chemistry.chemical_element, Article, Mice, In vivo, Cell Line, Tumor, Dendrimer, Oximes, Drug Discovery, Polyamines, Fluorescence microscope, Animals, Chelation, Chelating Agents, Integrin alphaVbeta3, Molecular Structure, Ligand (biochemistry), Fluorescence, chemistry, Biochemistry, Biophysics, Molecular Medicine, Female, Peptides |
| الوصف: | Ligand size and valency strongly influence the receptor uptake and clearance of tumor angiogenesis imaging agents. The structures of successful imaging agents exhibit a high degree of variability, encompassing small monovalent arginine-glycine-aspartic acid (RGD)-containing peptides, multivalent RGD-oligomers, and a monoclonal antibody against integrin alpha-v-beta-3 (alpha-v-beta-3). We have pursued a nanoscale approach to imaging of angiogenesis using rationally designed polyamidoamine (PAMAM) dendrimers covalently adorned with RGD-cyclopeptides. An orthogonal oxime-ligation strategy was applied to chemoselectively effect conjugation of the PAMAM dendrimers with RGD-cyclopeptides for targeting alpha vbeta 3. Fluorescent dyes for optical imaging and chelates for gadolinium-based magnetic resonance (MR) imaging were subsequently appended to create robust multimodal macromolecular imaging agents. Fluorescence microscopy revealed selective binding of the resulting RGD peptide-bearing dendrimer with empty chelates to alpha-v-beta-3-expressing cells, but somewhat reduced selectivity was observed following Gd(III) complexation. The expected incomplete saturation of chelates with Gd(III) ions permitted radiometal complexation, and an in vivo tissue distribution of the resulting agent in M21 melanoma tumor-bearing mice showed mostly renal and reticuloendothelial accumulation, with the tumor:blood ratio peaking (3.30+/-0.03) at 2 h postinjection. |
| تدمد: | 1543-8392 1543-8384 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d1477a19c1fa96bdcd6cc83c426489a4 https://doi.org/10.1021/mp800022a |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d1477a19c1fa96bdcd6cc83c426489a4 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15438392 15438384 |
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