EGFR-targeting Peptide Conjugated pH-sensitive Micelles as a Potential Drug Carrier for Photodynamic Detection and Therapy of Cancer

Cheng-Liang Peng, Yuan-I Chen, Ying-Hsia Shih, Tsai-Yueh Luo, Ming-Jium Shieh

Abstract

Multifunctional theranostics have recently been intensively explored to optimize the efficacy and safety. Herein, we report multifunctional micelle that constructed from graft copolymer PEGMA-co-PDPA and diblock copolymer mPEG-b-PCL as the carrier of hydrophobic photosensitizer, chlorin e6 (Ce6) for simultaneous fluorescence imaging and photodynamic therapy. The functional inner core of PEGMA-co-PDPA exhibited pH stimulate to accelerate drug release under slightly acidic microenvironments of tumors and the outer shell of micelles with epidermal growth factor receptor (EGFR)-targeting GE11 peptides for active targeting of EGFR-overexpressing cancer cells. The results demonstrate that GE11-conjugated chlorin e6-loaded micelles (GE11-Ce6-micelles) with particle size around 100 nm and the micelles had well defined core shell structure which was evaluated by TEM. In the in vitro cellular uptake studies, GE11-Ce6-micelles exhibited a higher amount of intracellular uptake of chlorin e6 in HCT116 cancer cells (EGFR high expression) via receptor-mediated endocytosis, in contrast with the time-dependent passive uptake of the non-targeted Ce6-micelles, thereby providing a effective photocytotoxic effect on the HCT116 cancer cells. In vivo study revealed that GE11-Ce6-micelles exhibited tumor targeting for photodynamic detection and excellent inhibition on tumor growth after irradiation, indicating that GE11-Ce6-micelles could be successfully applied to the effective fluorescence imaging and photodynamic therapy of cancer.

References

  1. Arteaga, C. L. 2002. Epidermal Growth Factor Receptor Dependence In Human Tumors: More Than Just Expression? The Oncologist, 7, 31-39.
  2. Chaw, C.-S., Chooi, K.-W., Liu, X.-M., Tan, C.-W., Wang, L. & Yang, Y.-Y. 2004. Thermally Responsive Core-Shell Nanoparticles Self-Assembled From Cholesteryl End-Capped And Grafted Polyacrylamides:: Drug Incorporation And In Vitro Release. Biomaterials, 25, 4297-4308.
  3. Huang, P., Xu, C., Lin, J., Wang, C., Wang, X. S., Zhang, C. L., Zhou, X. J., Guo, S. W. & Cui, D. X. 2011. Folic Acid-Conjugated Graphene Oxide Loaded With Photosensitizers For Targeting Photodynamic Therapy. Theranostics, 1, 240-250.
  4. Koo, H., Lee, H., Lee, S., Min, K. H., Kim, M. S., Lee, D. S., Choi, Y., Kwon, I. C., Kim, K. & Jeong, S. Y. 2010. In Vivo Tumor Diagnosis And Photodynamic Therapy Via Tumoral Ph-Responsive Polymeric Micelles. Chemical Communications, 46, 5668-5670.
  5. Lee, P.-C., Chiou, Y.-C., Wong, J.-M., Peng, C.-L. & Shieh, M.-J. 2013. Targeting Colorectal Cancer Cells With Single-Walled Carbon Nanotubes Conjugated To Anticancer Agent Sn-38 And Egfr Antibody. Biomaterials, 34, 8756-8765.
  6. Li, Z., Zhao, R., Wu, X., Sun, Y., Yao, M., Li, J., Xu, Y. & Gu, J. 2005. Identification And Characterization Of A Novel Peptide Ligand Of Epidermal Growth Factor Receptor For Targeted Delivery Of Therapeutics. The Faseb Journal, 19, 1978-1985.
  7. Milane, L., Duan, Z. & Amiji, M. 2010. Development Of Egfr-Targeted Polymer Blend Nanocarriers For Combination Paclitaxel/Lonidamine Delivery To Treat Multi-Drug Resistance In Human Breast And Ovarian Tumor Cells. Molecular Pharmaceutics, 8, 185-203.
  8. Min, K. H., Kim, J.-H., Bae, S. M., Shin, H., Kim, M. S., Park, S., Lee, H., Park, R.-W., Kim, I.-S., Kim, K., Kwon, I. C., Jeong, S. Y. & Lee, D. S. 2010. Tumoral Acidic Ph-Responsive Mpeg-Poly(?-Amino Ester) Polymeric Micelles For Cancer Targeting Therapy. Journal Of Controlled Release, 144, 259-266.
  9. Olivier, J.-C., Huertas, R., Lee, H. J., Calon, F. & Pardridge, W. M. 2002. Synthesis Of Pegylated Immunonanoparticles. Pharmaceutical Research, 19, 1137-1143.
  10. Peng, C.-L., Shieh, M.-J., Tsai, M.-H., Chang, C.-C. & Lai, P.-S. 2008a. Self-Assembled Star-Shaped Chlorin-Core Poly(?-Caprolactone)-Poly(Ethylene Glycol) Diblock Copolymer Micelles For Dual Chemo-Photodynamic Therapies. Biomaterials, 29, 3599-3608.
  11. Peng, C.-L., Yang, L.-Y., Luo, T.-Y., Lai, P.-S., Yang, S.- J., Lin, W.-J. & Shieh, M.-J. 2010. Development Of Ph Sensitive 2-(Diisopropylamino)Ethyl Methacrylate Based Nanoparticles For Photodynamic Therapy. Nanotechnology, 21, 155103.
  12. Peng, C. L., Lai, P. S., Lin, F. H., Wu, S. Y. H. & Shieh, M. J. 2009. Dual Chemotherapy And Photodynamic Therapy In An Ht-29 Human Colon Cancer Xenograft Model Using Sn-38-Loaded Chlorin-Core Star Block Copolymer Micelles. Biomaterials, 30, 3614-3625.
  13. Peng, C. L., Shieh, M. J., Tsai, M. H., Chang, C. C. & Lai, P. S. 2008b. Self-Assembled Star-Shaped ChlorinCore Poly(C-Caprolactone)-Poly(Ethylene Glycol) Diblock Copolymer Micelles For Dual ChemoPhotodynamic Therapies. Biomaterials, 29, 3599- 3608.
  14. Schmidt-Erfurth, U. & Hasan, T. 2000. Mechanisms Of Action Of Photodynamic Therapy With Verteporfin For The Treatment Of Age-Related Macular Degeneration. Survey Of Ophthalmology, 45, 195- 214.
  15. Shen, Y., Tang, H., Radosz, M., Van Kirk, E. & Murdoch, W. 2008. Ph-Responsive Nanoparticles For Cancer Drug Delivery. In: Jain, K. (Ed.) Drug Delivery Systems. Humana Press.
  16. Wang, M., Chen, Z., Zheng, W., Zhu, H., Lu, S., Ma, E., Tu, D., Zhou, S., Huang, M. & Chen, X. 2014a. Lanthanide-Doped Upconversion Nanoparticles Electrostatically Coupled With Photosensitizers For Near-Infrared-Triggered Photodynamic Therapy. Nanoscale, 6, 8274-8282.
  17. Wang, X., Liu, K., Yang, G., Cheng, L., He, L., Liu, Y., Li, Y., Guo, L. & Liu, Z. 2014b. Near-Infrared Light Triggered Photodynamic Therapy In Combination With Gene Therapy Using Upconversion Nanoparticles For Effective Cancer Cell Killing. Nanoscale.
  18. Zhang, G.-D., Harada, A., Nishiyama, N., Jiang, D.-L., Koyama, H., Aida, T. & Kataoka, K. 2003. Polyion Complex Micelles Entrapping Cationic Dendrimer Porphyrin: Effective Photosensitizer For Photodynamic Therapy Of Cancer. Journal Of Controlled Release, 93, 141-150.
Download


Paper Citation


in Harvard Style

Peng C., Chen Y., Shih Y., Luo T. and Shieh M. (2016). EGFR-targeting Peptide Conjugated pH-sensitive Micelles as a Potential Drug Carrier for Photodynamic Detection and Therapy of Cancer . In Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 2: BIOIMAGING, (BIOSTEC 2016) ISBN 978-989-758-170-0, pages 105-110. DOI: 10.5220/0005774201050110


in Bibtex Style

@conference{bioimaging16,
author={Cheng-Liang Peng and Yuan-I Chen and Ying-Hsia Shih and Tsai-Yueh Luo and Ming-Jium Shieh},
title={EGFR-targeting Peptide Conjugated pH-sensitive Micelles as a Potential Drug Carrier for Photodynamic Detection and Therapy of Cancer},
booktitle={Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 2: BIOIMAGING, (BIOSTEC 2016)},
year={2016},
pages={105-110},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0005774201050110},
isbn={978-989-758-170-0},
}


in EndNote Style

TY - CONF
JO - Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 2: BIOIMAGING, (BIOSTEC 2016)
TI - EGFR-targeting Peptide Conjugated pH-sensitive Micelles as a Potential Drug Carrier for Photodynamic Detection and Therapy of Cancer
SN - 978-989-758-170-0
AU - Peng C.
AU - Chen Y.
AU - Shih Y.
AU - Luo T.
AU - Shieh M.
PY - 2016
SP - 105
EP - 110
DO - 10.5220/0005774201050110