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The promotion of siRNA delivery to breast cancer overexpressing epidermal growth factor receptor through anti-EGFR antibody conjugation by immunoliposomes

Paper ID Volume ID Publish Year Pages File Format Full-Text
7713 561 2011 12 PDF Available
Title
The promotion of siRNA delivery to breast cancer overexpressing epidermal growth factor receptor through anti-EGFR antibody conjugation by immunoliposomes
Abstract

The LPD (liposome-polycation-DNA complex) is an effective nanovector for systemically small interfering RNA (siRNA) delivery which was well characterized previously. However, little effort was spend on the development of targeted LPD conjugated with tumor specific antibody (TLPD) which would be potent in promoting siRNA delivery in tumor. Here, we prepared TLPD through a self-assembling process followed by anti-EGFR antibody conjugation. The effect of antibody type, conjugation strategy and amount on the physicochemical and biological properties of TLPD was investigated. We obtained optimized TLPD conjugated with anti-EGFR Fab’ by conventional conjugation (TLPD-FCC), which possessed a small size around 150 nm and superior in vitro stability. Compared with nontargeted LPD (NTLPD), TLPD-FCC showed significantly enhanced binding affinity and luciferase gene silencing activity in EGFR overexpressing MDA-MB-231 breast cancer cells in vitro. Moreover, the in vivo accumulation of TLPD-FCC was obviously higher than that of NTLPD in MDA-MB-231 tumor 24 h post intravenous injection. The promoted uptake of TLPD-FCC in MDA-MB-231 tumor was further confirmed by confocal microscopy. Notably, three intravenous injections of siRNA in TLPD-FCC significantly silenced luciferase expression by ∼20%, whereas NTLPD showed little effect. All these results suggested that our TLPD-FCC have a great potential in delivering siRNA to EGFR overexpressing breast cancers.

Keywords
Antibody; EGFR; Gene silencing; PEG; siRNA delivery
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The promotion of siRNA delivery to breast cancer overexpressing epidermal growth factor receptor through anti-EGFR antibody conjugation by immunoliposomes
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 13, May 2011, Pages 3459–3470
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us