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Effect of trastuzumab-modified antisense oligonucleotide-loaded human serum albumin nanoparticles prepared by heat denaturation

Paper ID Volume ID Publish Year Pages File Format Full-Text
9224 621 2008 7 PDF Available
Title
Effect of trastuzumab-modified antisense oligonucleotide-loaded human serum albumin nanoparticles prepared by heat denaturation
Abstract

Nanoparticles represent a promising tool for targeted drug delivery to tumour cells and are able to protect drugs against degradation. In our present study we developed targeted nanoparticles loaded with antisense oligonucleotides (ASOs) against Plk1 (polo-like kinase 1) prepared by heat denaturation instead of using glutaraldehyde. Glutaraldehyde can lead to an inactivation of ASOs through chemical crosslinking and is a toxic entity. We examined the ideal preparation conditions and characterised the resulting particles in terms of physico-chemical properties, ASO recovery after enzymatic degradation and stability. Stable monodisperse nanoparticles with an ASO recovery of more than 80% could be prepared at a temperature of 105 °C for 10 min.Furthermore we performed quantitative real-time PCR and Western blot to detect an ASO-mediated effect on Plk1 in BT-474 cells. We observed a significant reduction of Plk1 mRNA and protein expression. Thus, this is the first report of ASO-loaded HSA nanoparticles prepared by heat denaturation, where an impact on gene expression could be observed. The data provide the basis for the further development of carrier systems for ASOs to reduce off-target effects evoked by systemically administered ASOs and to achieve a better penetration into primary and metastatic target cells.

Keywords
Albumin; Nanoparticle; Antisense; Drug delivery; Polo-like kinase 1; Heat stabilisation
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Effect of trastuzumab-modified antisense oligonucleotide-loaded human serum albumin nanoparticles prepared by heat denaturation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 29, Issue 29, October 2008, Pages 4022–4028
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