Angewandte Chemie International EditionVolume 43, Issue 46 p. 6323-6327 Communication cRGD-Functionalized Polymer Micelles for Targeted Doxorubicin Delivery† Norased Nasongkla, Norased Nasongkla Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969 These authors contributed equally to this workSearch for more papers by this authorXintao Shuai Dr., Xintao Shuai Dr. Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969 These authors contributed equally to this workSearch for more papers by this authorHua Ai Dr., Hua Ai Dr. Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969Search for more papers by this authorBrent D. Weinberg, Brent D. Weinberg Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969Search for more papers by this authorJohn Pink Dr., John Pink Dr. Department of Radiation Oncology, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USASearch for more papers by this authorDavid A. Boothman Prof., David A. Boothman Prof. Department of Radiation Oncology, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USASearch for more papers by this authorJinming Gao Prof. Dr., Jinming Gao Prof. Dr. [email protected] Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969Search for more papers by this author Norased Nasongkla, Norased Nasongkla Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969 These authors contributed equally to this workSearch for more papers by this authorXintao Shuai Dr., Xintao Shuai Dr. Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969 These authors contributed equally to this workSearch for more papers by this authorHua Ai Dr., Hua Ai Dr. Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969Search for more papers by this authorBrent D. Weinberg, Brent D. Weinberg Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969Search for more papers by this authorJohn Pink Dr., John Pink Dr. Department of Radiation Oncology, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USASearch for more papers by this authorDavid A. Boothman Prof., David A. Boothman Prof. Department of Radiation Oncology, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USASearch for more papers by this authorJinming Gao Prof. Dr., Jinming Gao Prof. Dr. [email protected] Department of Biomedical Engineering, Case Western Reserve University, 10 900 Euclid Avenue, Cleveland, Ohio 44 106, USA, Tel: (+1) 216-368-1083, Fax: (+1) 216-368-4969Search for more papers by this author First published: 23 November 2004 https://doi.org/10.1002/anie.200460800Citations: 345 † This research is supported by the National Institutes of Health (R01-CA-90 696). N.N. acknowledges the Royal Thai Government for a predoctoral fellowship support. X.T.S. acknowledges fellowship support from the Ohio Biomedical Research and Technology Trust fund. We thank Dr. Steven Eppell and Zhilei Liu for their help with atomic force microscopy. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract Targeting micelles: Cyclic pentapeptide cRGDfK (red triangles), which targets integrin αvβ3, was conjugated to the outer shell of doxorubicin-loaded (red hexagons) polymeric micelles by using a post-micelle modification method. The modified micelles significantly enhanced their internalization (up to 30-fold) by receptor-mediated endocytosis in tumor endothelial cells overexpressing the αvβ3 receptor. Supporting Information Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460800_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1A. M. Fernandez, K. Van Derpoorten, L. Dasnois, K. Lebtahi, V. Dubois, T. J. Lobl, S. Gangwar, C. Oliyai, E. R. Lewis, D. Shochat, A. Trouet, J. Med. Chem. 2001, 44, 3750–3753. 10.1021/jm0108754 CASPubMedWeb of Science®Google Scholar 2M. Yokoyama, T. Okano, Y. Sakurai, H. Ekimoto, C. Shibazaki, K. Kataoka, Cancer Res. 1991, 51, 3229–3236. CASPubMedWeb of Science®Google Scholar 3K. Kataoka, T. Matsumoto, M. Yokoyama, T. Okano, Y. Sakurai, S. Fukushima, K. Okamoto, G. S. Kwon, J. Controlled Release 2000, 64, 143–153. 10.1016/S0168-3659(99)00133-9 CASPubMedWeb of Science®Google Scholar 4R. Savic, L. Luo, A. Eisenburg, D. Maysinger, Science 2003, 300, 615–618. 10.1126/science.1078192 CASPubMedWeb of Science®Google Scholar 5G. S. Kwon, K. Kataoka, Adv. Drug Delivery Rev. 1995, 16, 295–309. 10.1016/0169-409X(95)00031-2 CASWeb of Science®Google Scholar 6K. Kataoka, A. Harada, Y. Nagasaki, Adv. Drug Delivery Rev. 2001, 47, 113–131. 10.1016/S0169-409X(00)00124-1 CASPubMedWeb of Science®Google Scholar 7R. Haag, Angew. Chem. 2004, 116, 280–284; 10.1002/ange.200301694 Google ScholarAngew. Chem. Int. Ed. 2004, 43, 278–282; . 10.1002/anie.200301694 CASPubMedWeb of Science®Google Scholar 8Y. Bae, S. Fukushima, A. Harada, K. Kataoka, Angew. Chem. 2003, 115, 4788–4791; 10.1002/ange.200250653 Google ScholarAngew. Chem. Int. Ed. 2003, 42, 4640–4643; . 10.1002/anie.200250653 CASPubMedWeb of Science®Google Scholar 9K. Greish, J. Fang, T. Inustuka, A. Nagamitsu, H. Maeda, Clin. Eur. Clin. Phamarcokinet. 2003, 42, 1089–1105. 10.2165/00003088-200342130-00002 CASPubMedWeb of Science®Google Scholar 10Y. Yamamoto, Y. Nagasaki, Y. Kato, Y. Sugiyama, K. Kataoka, J. Controlled Release 2001, 77, 27–38. 10.1016/S0168-3659(01)00451-5 CASPubMedWeb of Science®Google Scholar 11D. Needham, M. W. Dewhirst, Adv. Drug Delivery Rev. 2001, 53, 285–305. 10.1016/S0169-409X(01)00233-2 CASPubMedWeb of Science®Google Scholar 12G. D. Yancopoulos, M. Klagsbrun, J. Folkman, Cell 1998, 93, 661–664. 10.1016/S0092-8674(00)81426-9 CASPubMedWeb of Science®Google Scholar 13B. P. Eliceiri, D. A. Cheresh, Curr. Opin. Cell Biol. 2001, 13, 563–568. 10.1016/S0955-0674(00)00252-0 CASPubMedWeb of Science®Google Scholar 14P. C. Brooks, A. M. Montgomery, M. Rosenfeld, R. A. Reisfeld, T. Hu, G. Klier, D. A. Cheresh, Cell 1994, 79, 1157–1164. 10.1016/0092-8674(94)90007-8 CASPubMedWeb of Science®Google Scholar 15T. J. Wickham, Nature Med. 2003, 9, 135–139. 10.1038/nm0103-135 CASPubMedWeb of Science®Google Scholar 16J. D. Hood, M. Bednarski, R. Frausto, S. Guccione, R. A. Reisfeld, R. Xiang, D. A. Cheresh, Science 2002, 296, 2404–2407. 10.1126/science.1070200 CASPubMedWeb of Science®Google Scholar 17V. P. Torchilin, A. N. Lukyanov, Z. Gao, B. Papahadjopoulos-Sternberg, Proc. Natl. Acad. Sci. USA 2003, 100, 6039–6044. 10.1073/pnas.0931428100 CASPubMedWeb of Science®Google Scholar 18E. S. Lee, K. Na, Y. H. Bae, J. Controlled Release 2003, 91, 103–113. 10.1016/S0168-3659(03)00239-6 CASPubMedWeb of Science®Google Scholar 19R. Haubner, R. Gratias, B. Diefenbach, S. L. Goodman, A. Jonczyk, H. Kessler, J. Am. Chem. Soc. 1996, 118, 7461–7472. 10.1021/ja9603721 CASWeb of Science®Google Scholar 20M. Kantlehner, D. Finsinger. J. Meyer, P. Schaffner, A. Jonczyk. B. Diefenbach, B. Nies, H. Kessler, Angew. Chem. 1999, 111, 587–590; 10.1002/(SICI)1521-3757(19990215)111:4<587::AID-ANGE587>3.0.CO;2-N Google ScholarAngew. Chem. Int. Ed. 1999, 38, 560–562; . 10.1002/(SICI)1521-3773(19990215)38:4<560::AID-ANIE560>3.0.CO;2-F CASPubMedWeb of Science®Google Scholar 21W. Arap, R. Pasqualini, E. Ruoslahti, Science 1998, 279, 377–380. 10.1126/science.279.5349.377 CASPubMedWeb of Science®Google Scholar 22X. Shuai, T. Merdan, A. K. Schaper, F. Xi, T. Kissel, Bioconjugate Chem. 2004, 15, 441–448. 10.1021/bc034113u CASPubMedWeb of Science®Google Scholar 23X. Shuai, H. Ai, N. Nasongkla, S. Kim, J. Gao, J. Controlled Release 2004, 98, 415–426. 10.1016/j.jconrel.2004.06.003 CASPubMedWeb of Science®Google Scholar 24D. L. Wilson, K. S. Kump, S. J. Eppell, R. E. Marchant, Langmuir 1995, 11, 265–272. 10.1021/la00001a045 CASWeb of Science®Google Scholar 25W. A. Ducker, T. J. Senden, R. M. Pashley, Nature 1991, 353, 239–241. 10.1038/353239a0 CASWeb of Science®Google Scholar 26B. A. Todd, S. J. Eppell, Surf. Sci. 2001, 491, 473–483. 10.1016/S0039-6028(01)01313-9 CASWeb of Science®Google Scholar 27F. Samaniego, D. Young, C. Grimes, V. Prospero, M. Christofidou-Solomidou, H. M. Delisser, O. Prakash, A. A. Sahin, S. Wang, Cell Growth Differ. 2002, 13, 387–395. CASPubMedWeb of Science®Google Scholar 28K. Kunath, T. Merdan, O. Hegener, H. Häberlein, T. Kissel, J. Gene Med. 2003, 5, 588–599. 10.1002/jgm.382 CASPubMedWeb of Science®Google Scholar Citing Literature Volume43, Issue46November 26, 2004Pages 6323-6327 ReferencesRelatedInformation