F3 peptide-functionalized PEG-PLA nanoparticles co-administrated with tLyp-1 peptide for anti-glioma drug delivery.

Abstract

The development of a drug delivery strategy which can mediate efficient tumor targeting together with high cellular internalization and extensive vascular extravasation is essential and important for glioma treatment. To achieve this goal, F3 peptide that specifically bind to nucleolin, which is highly expressed on the surface of both glioma cells and endothelial cells of glioma angiogenic blood vessels, is utilized to decorate a nanoparticulate drug delivery system to realize glioma cell and neovasculature dual-targeting and efficient cellular internalization. Tumor homing and penetrating peptide, tLyp-1 peptide, which contains the motif of (R/K)XX(R/K) and specially binds to neuropilin is co-administrated to improve the penetration of the nanoparticles across angiogenic vasculature into glioma parenchyma. The F3 conjugation via a maleimide-thiol coupling reaction was confirmed by XPS analysis with 1.03% nitrogen detected on the surface of the functionalized nanoparticles. Enhanced cellular interaction with C6 cells, improved penetration in 3D multicell tumor spheroids, and increased cytotoxicity of the loaded paclitaxel were achieved by the F3-functionalized nanoparticles (F3-NP). Following co-administration with tLyp-1 peptide, F3-NP displayed enhanced accumulation at the tumor site and deep penetration into the glioma parenchyma and achieved the longest survival in mice bearing intracranial C6 glioma. The findings here clearly indicated that the strategy by co-administrating a tumor homing and penetrating peptide with functionalized nanoparticles dual-targeting both glioma cells and neovasculature could significantly improve the anti-glioma drug delivery, which also hold a great promise for chemotherapy of other hard-to-cure cancers.

• Authors: Quanyin Hu, Guangzhi Gu, Zhongyang Liu, Mengyin Jiang, Ting Kang, Deyu Miao, Yifan Tu, Zhiqing Pang, Qingxiang Song, Lei Yao, Huimin Xia, Hongzhan Chen, Xinguo Jiang, Xiaoling Gao, Jun Chen
• Journal: Biomaterials (Biomaterials) Vol. 34 Issue 4 Pg. 1135-45 (Jan 2013) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 23146434 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• LyP-1 peptide
• Nanocapsules
• Peptides
• Peptides, Cyclic
• monomethoxypolyethyleneglycol-polylactide block copolymer
• Polyethylene Glycols
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, chemistry)
• Brain Neoplasms (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Glioma (drug therapy, metabolism, pathology)
• Mice
• Mice, Nude
• Nanocapsules (administration & dosage, chemistry)
• Paclitaxel (administration & dosage, chemistry)
• Peptides (chemistry, pharmacokinetics)
• Peptides, Cyclic (chemistry, pharmacokinetics)
• Polyethylene Glycols (chemistry)
• Rats
• Treatment Outcome