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Research Article

Impact of PEGylation on biodistribution and tumor accumulation of Lipid-Mu peptide-DNA

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Pages 1-10 | Received 26 Feb 2012, Accepted 30 Jun 2012, Published online: 19 Oct 2012
 

Abstract

For gene-based therapeutic approaches that require transfection of specific cell targets in vivo, it is important to design the delivery system to have optimized tissue distribution. Surface PEGylation of liposomes and polymer nanoparticles has been shown to lead to prolonged blood circulation and also preferential accumulation in tumor sites resulting from the enhanced permeability and retention (EPR) effect. The aim of this study was to investigate the effect of different surface PEGylation densities on resulted biodistribution profiles of Lipid-Mu peptide-DNA (LMD) nanoparticles. LMD particles containing the near infrared fluorescent lipid dye, Cy5.5-DSPE, were injected intravenously, and whole-body fluorescence images of the live animal were recorded. Analysis of these time series of images indicated that LMDs with different surface PEG2000 densities had distinctively different biodistribution and tumor accumulation profiles. LMDs containing approximately 15–25% of surface PEG2000 were shown to have the highest accumulation and longest residence time in tumor. LMD distribution and pharmacokinetic profiles in other organs were also observed to be different and were analyzed.

Acknowledgments

The authors thank Ming Yao for providing support for the H460 human tumor xenograft mice and Meilin Song for the work on the image-based pharmacokinetic analysis.

Declaration of interest

This study was supported by the National Science Fund for Distinguished Young Scholars (grant no. 30825045) and the Shanghai Committee of Science and Technology (grant no. 08431902100).

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