NDLI: Cyclic RGD-polyethylene glycol-polyethylenimine for intracranial glioblastoma-targeted gene delivery.

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Cyclic RGD-polyethylene glycol-polyethylenimine for intracranial glioblastoma-targeted gene delivery.

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Cyclic RGD-polyethylene glycol-polyethylenimine for intracranial glioblastoma-targeted gene delivery.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zhan, Changyou Meng, Qinggang Li, Qinghua Feng, Linglin Zhu, Jianhua Lu, Weiyue
Description	Country affiliation: China Author Affiliation: Zhan C ( School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, Shanghai, China.)
Abstract	Even though the blood-brain barrier (BBB) is compromised for angiogenesis, therapeutic agents for glioblastoma multiforme (GBM) are particularly inefficient due to the existence of a blood-tumor barrier (BTB), which hampers tumor accumulation and uptake. Integrin (v)ß(3) is overexpressed on glioblastoma U87 cells and neovasculture, thus making its ligands such as the RGD motif target glioblastoma in vitro and in vivo. In the present work, we have designed a modified polyethylene glycol-polyethylenimine (PEG-PEI) gene carrier by conjugating it with a cyclic RGD sequence, c(RGDyK) (cyclic arginine-glycine-aspartic acid-D-tyrosine-lysine). When complexed with plasmid DNA, this gene carrier, termed RGD-PEG-PEI, formed homogenous nanoparticles with a mean diameter of 73ânm. These nanoparticles had a high binding affinity with U87 cells and facilitated targeted gene delivery against intracranial glioblastoma in vivo, thereby leading to a higher gene transfer efficiency compared to the PEG-PEI gene carrier without RGD decoration. This intracranial glioblastoma-targeted gene carrier also enhanced the therapeutic efficacy of pORF-hTRAIL, as evidenced by a significantly prolonged survival of intracranial glioblastoma-bearing nude mice. Considering the contribution of glioblastoma neovasculature to the BBB under angiogenic conditions, our results demonstrated the therapeutic feasibility of treating a brain tumor through mediation of integrin (v)ß(3), as well as the potential of using RGD-PEG-PEI as a targeted gene carrier in the treatment of intracranial glioblastoma.
File Format	HTM / HTML
ISSN	18614728
Issue Number	1
Volume Number	7
e-ISSN	1861471X
Journal	Chemistry - An Asian Journal
Language	English
Publisher	Wiley-VCH
Publisher Date	2012-01-02
Publisher Place	Germany
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Polyethyleneimine Gene Transfer Techniques Research Support, Non-u.s. Gov't Polyethylene Glycols Humans Glioblastoma Mice, Inbred Balb C Male Journal Article Brain Neoplasms Peptides, Cyclic Chemistry Animals Mice, Nude Cell Line, Tumor Discipline Chemistry Genetics Mice
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry

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