HDL-Mimicking Peptide–Lipid Nanoparticles with Improved Tumor Targeting
Zhihong Zhang
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
These authors contributed equally to this work.
Search for more papers by this authorJuan Chen
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
These authors contributed equally to this work.
Search for more papers by this authorLili Ding
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorHonglin Jin
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
Search for more papers by this authorJonathan F. Lovell
Institute for Biomaterials and Biomedical Engineering University of Toronto Toronto (Canada)
Search for more papers by this authorIan R. Corbin
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorWeiguo Cao
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Department of Chemistry Shanghai University Shanghai (China)
Search for more papers by this authorPui-Chi Lo
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorMi Yang
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorMing-Sound Tsao
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorQingming Luo
Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
Search for more papers by this authorCorresponding Author
Gang Zheng
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Institute for Biomaterials and Biomedical Engineering University of Toronto Toronto (Canada)
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada).Search for more papers by this authorZhihong Zhang
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
These authors contributed equally to this work.
Search for more papers by this authorJuan Chen
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
These authors contributed equally to this work.
Search for more papers by this authorLili Ding
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorHonglin Jin
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
Search for more papers by this authorJonathan F. Lovell
Institute for Biomaterials and Biomedical Engineering University of Toronto Toronto (Canada)
Search for more papers by this authorIan R. Corbin
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorWeiguo Cao
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Department of Chemistry Shanghai University Shanghai (China)
Search for more papers by this authorPui-Chi Lo
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorMi Yang
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorMing-Sound Tsao
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Search for more papers by this authorQingming Luo
Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics Huazhong University of Science and Technology Wuhan (China)
Search for more papers by this authorCorresponding Author
Gang Zheng
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada)
Institute for Biomaterials and Biomedical Engineering University of Toronto Toronto (Canada)
Department of Medical Biophysics Ontario Cancer Institute University of Toronto TMDT 5-363, 101 College Street, Toronto, ON M5G 1L7 (Canada).Search for more papers by this authorAbstract
Targeted delivery of intracellularly active diagnostics and therapeutics in vivo is a major challenge in cancer nanomedicine. A nanocarrier should possess long circulation time yet be small and stable enough to freely navigate through interstitial space to deliver its cargo to targeted cells. Herein, it is shown that by adding targeting ligands to nanoparticles that mimic high-density lipoprotein (HDL), tumor-targeted sub-30-nm peptide–lipid nanocarriers are created with controllable size, cargo loading, and shielding properties. The size of the nanocarrier is tunable between 10 and 30 nm, which correlates with a payload of 15–100 molecules of fluorescent dye. Ligand-directed nanocarriers targeting epidermal growth factor receptor (EGFR) are confirmed both in vitro and in vivo. The nanocarriers show favorable circulation time, tumor accumulation, and biodistribution with or without the targeting ligand. The EGFR targeting ligand is proved to be essential for the EGFR-mediated tumor cell uptake of the nanocarriers, a prerequisite of intracellular delivery. The results demonstrate that targeted HDL-mimetic nanocarriers are useful delivery vehicles that could open new avenues for the development of clinically viable targeted nanomedicine.
Supporting Information
Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors.
| Filename | Description |
|---|---|
| smll_200901515_sm_supplfigs.pdf390.9 KB | supplfigs |
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
- 1 T. M. Allen, P. R. Cullis, Science 2004, 303, 1818.
- 2 M. E. Davis, Z. G. Chen, D. M. Shin, Nat. Rev. Drug Discovery 2008, 7, 771.
- 3 L. Zhang, F. X. Gu, J. M. Chan, A. Z. Wang, R. S. Langer, O. C. Farokhzad, Clin. Pharmacol. Ther. 2008, 83, 761.
- 4 A. Pluen, Y. Boucher, S. Ramanujan, T. D. McKee, T. Gohongi, E. di Tomaso, E. B. Brown, Y. Izumi, R. B. Campbell, D. A. Berk, R. K. Jain, Proc. Natl. Acad. Sci. USA 2001, 98, 4628.
- 5 V. P. Torchilin, Pharm. Res. 2007, 24, 1.
- 6 N. Tang, G. Du, N. Wang, C. Liu, H. Hang, W. Liang, J. Natl. Cancer Inst. 2007, 99, 1004.
- 7 E. C. Cho, J. Xie, P. A. Wurm, Y. Xia, Nano Lett. 2009, 9, 1080.
- 8 H. S. Choi, W. Liu, P. Misra, E. Tanaka, J. P. Zimmer, B. Itty Ipe, M. G. Bawendi, J. V. Frangioni, Nat. Biotechnol. 2007, 25, 1165.
- 9 H. C. Fischer, W. C. Chan, Curr. Opin. Biotechnol. 2007, 18, 565.
- 10 H. Wang, X. Chen, Expert Opin. Drug Delivery 2009, 6, 745.
- 11 W. Jiang, B. Y. Kim, J. T. Rutka, W. C. Chan, Nat. Nanotechnol. 2008, 3, 145.
- 12 X. Gao, Y. Cui, R. M. Levenson, L. W. Chung, S. Nie, Nat. Biotechnol. 2004, 22, 969.
- 13 P. C. Rensen, R. L. de Vrueh, J. Kuiper, M. K. Bijsterbosch, E. A. Biessen, T. J. van Berkel, Adv. Drug Delivery Rev. 2001, 47, 251.
- 14 I. R. Corbin, J. Chen, W. Cao, H. Li, S. Lund-Katz, G. Zheng, J. Biomed. Nanotechnol. 2007, 3, 367.
- 15 J. C. Frias, K. J. Williams, E. A. Fisher, Z. A. Fayad, J. Am. Chem. Soc. 2004, 126, 16316.
- 16 S. Eisenberg, H. G. Windmueller, R. I. Levy, J. Lipid Res. 1973, 14, 446.
- 17 W. H. Daerr, W. Pethke, E. T. Windler, H. Greten, Biochim. Biophys. Acta 1990, 1043, 311.
- 18 L. T. Bloedon, R. Dunbar, D. Duffy, P. Pinell-Salles, R. Norris, B. J. DeGroot, R. Movva, M. Navab, A. M. Fogelman, D. J. Rader, J. Lipid Res. 2008, 49, 1344.
- 19 G. Giaccone, Ann. Oncol. 2005, 16, 538.
- 20 S. Acton, A. Rigotti, K. T. Landschulz, S. Xu, H. H. Hobbs, M. Krieger, Science 1996, 271, 518.
- 21 A. V. Bocharov, I. N. Baranova, T. G. Vishnyakova, A. T. Remaley, G. Csako, F. Thomas, A. P. Patterson, T. L. Eggerman, J. Biol. Chem. 2004, 279, 36072.
- 22 D. B. Kirpotin, D. C. Drummond, Y. Shao, M. R. Shalaby, K. Hong, U. B. Nielsen, J. D. Marks, C. C. Benz, J. W. Park, Cancer Res. 2006, 66, 6732.
- 23 D. N. Amin, D. R. Bielenberg, E. Lifshits, J. V. Heymach, M. Klagsbrun, Microvasc. Res. 2008, 76, 15.
- 24 D. N. Amin, K. Hida, D. R. Bielenberg, M. Klagsbrun, Cancer Res. 2006, 66, 2173.
- 25 M. Nikanjam, E. A. Blakely, K. A. Bjornstad, X. Shu, T. F. Budinger, T. M. Forte, Int. J. Pharm. 2007, 328, 86.
- 26 I. R. Corbin, G. Zheng, Nanomedicine 2007, 2, 375.
- 27 K. Wang, X. Yan, Y. Cui, Q. He, J. Li, Bioconjugate Chem. 2007, 18, 1735.
- 28 M. R. Dreher, W. Liu, C. R. Michelich, M. W. Dewhirst, F. Yuan, A. Chilkoti, J. Natl. Cancer Inst. 2006, 98, 335.
- 29 S. D. Perrault, C. Walkey, T. Jennings, H. C. Fischer, W. C. Chan, Nano Lett. 2009, 9, 1909.
- 30 G. Zheng, J. Chen, H. Li, J. D. Glickson, Proc. Natl. Acad. Sci. USA 2005, 102, 17757.
- 31 J. Chen, I. R. Corbin, H. Li, W. Cao, J. D. Glickson, G. Zheng, J. Am. Chem. Soc. 2007, 129, 5798.
- 32 Z. Li, R. Zhao, X. Wu, Y. Sun, M. Yao, J. Li, Y. Xu, J. Gu, FASEB J. 2005, 19, 1978.
- 33 S. M. Stephenson, P. S. Low, R. J. Lee, Methods Enzymol. 2004, 387, 33.
- 34 V. K. Mishra, G. M. Anantharamaiah, J. P. Segrest, M. N. Palgunachari, M. Chaddha, S. W. Sham, N. R. Krishna, J. Biol. Chem. 2006, 281, 6511.
- 35 J. Chu, Z. Zhang, Y. Zheng, J. Yang, L. Qin, J. Lu, Z. Huang, S. Zhen, Q. Luo, Biosens. Bioelectron. 2009, 25, 234.
