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

被引:186
作者
Hu, Quanyin [1 ]
Gu, Guangzhi [1 ]
Liu, Zhongyang [1 ]
Jiang, Mengyin [4 ]
Kang, Ting [1 ]
Miao, Deyu [4 ]
Tu, Yifan [1 ]
Pang, Zhiqing [1 ]
Song, Qingxiang [2 ]
Yao, Lei [2 ]
Xia, Huimin [1 ,3 ]
Chen, Hongzhan [2 ]
Jiang, Xinguo [1 ]
Gao, Xiaoling [2 ]
Chen, Jun [1 ]
机构
[1] Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ & PLA, Shanghai 201203, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Inst Med Sci, Dept Pharmacol, Shanghai 200025, Peoples R China
[3] SIFDC, Shanghai 201203, Peoples R China
[4] Shandong Univ Tradit Chinese Med, Sch Pharm, Jinan, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
F3; peptide; tLyp-1; Co-administration; Nanoparticle; Paclitaxel; Anti-glioma; BRAIN-TUMORS; IN-VIVO; POLYMERIC NANOPARTICLES; THERAPEUTIC AGENTS; ENDOTHELIAL-CELLS; SOLID TUMORS; PACLITAXEL; GLIOMA; NANOCARRIERS; GLIOBLASTOMA;
D O I
10.1016/j.biomaterials.2012.10.048
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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 B 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. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1135 / 1145
页数:11
相关论文
共 49 条
[1]   Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26 [J].
Aktas, Y ;
Yemisci, M ;
Andrieux, K ;
Gürsoy, RN ;
Alonso, MJ ;
Fernandez-Megia, E ;
Novoa-Carballal, R ;
Quiñoá, E ;
Riguera, R ;
Sargon, MF ;
Çelik, HH ;
Demir, AS ;
Hincal, AA ;
Dalkara, T ;
Çapan, Y ;
Couvreur, P .
BIOCONJUGATE CHEMISTRY, 2005, 16 (06) :1503-1511
[2]   Factors affecting the clearance and biodistribution of polymeric nanoparticles [J].
Alexis, Frank ;
Pridgen, Eric ;
Molnar, Linda K. ;
Farokhzad, Omid C. .
MOLECULAR PHARMACEUTICS, 2008, 5 (04) :505-515
[3]   Active targeting of brain tumors using nanocarriers [J].
Beduneau, Arnaud ;
Saulnier, Patrick ;
Benoit, Jean-Pierre .
BIOMATERIALS, 2007, 28 (33) :4947-4967
[4]   Primary brain tumours in adults [J].
Behin, A ;
Hoang-Xuan, K ;
Carpentier, AF ;
Delattre, JY .
LANCET, 2003, 361 (9354) :323-331
[5]   Nanocarriers to Solid Tumors: Considerations on Tumor Penetration and Exposure of Tumor Cells to Therapeutic Agents [J].
Bhagat, Manali ;
Halligan, Susan ;
Sofou, Stavroula .
CURRENT PHARMACEUTICAL BIOTECHNOLOGY, 2012, 13 (07) :1306-1316
[6]   Nanomaterial-mediated CNS delivery of diagnostic and therapeutic agents [J].
Biddlestone-Thorpe, Laura ;
Marchi, Nicola ;
Guo, Kathy ;
Ghosh, Chaitali ;
Janigro, Damir ;
Valerie, Kristoffer ;
Yang, Hu .
ADVANCED DRUG DELIVERY REVIEWS, 2012, 64 (07) :605-613
[7]   Functions of lipid rafts in biological membranes [J].
Brown, DA ;
London, E .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1998, 14 :111-136
[8]   Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels [J].
Christian, S ;
Pilch, J ;
Akerman, ME ;
Porkka, K ;
Laakkonen, P ;
Ruoslahti, E .
JOURNAL OF CELL BIOLOGY, 2003, 163 (04) :871-878
[9]   Impact of Nanotechnology on Drug Delivery [J].
Farokhzad, Omid C. ;
Langer, Robert .
ACS NANO, 2009, 3 (01) :16-20
[10]   The association of autophagy with polyethylenimine-induced cytotoxity in nephritic and hepatic cell lines [J].
Gao, Xiaoling ;
Yao, Lei ;
Song, Qiangxiang ;
Zhu, Liang ;
Xia, Zheng ;
Xia, Huimin ;
Jiang, Xinguo ;
Chen, Jun ;
Chen, Hongzhuan .
BIOMATERIALS, 2011, 32 (33) :8613-8625