Issue 7, 2015

Balancing polymer hydrophobicity for ligand presentation and siRNA delivery in dual function CXCR4 inhibiting polyplexes

Abstract

In the present study, a series of copolymers (PAMD-Ch) was synthesized by grafting polymeric Plerixafor/AMD3100 (PAMD) with different amounts of cholesterol and the effect of cholesterol modification on siRNA delivery was investigated. PAMD-Ch/siRNA polyplexes exhibited improved colloidal and enzymatic stability when compared with PAMD/siRNA polyplexes containing no cholesterol. PAMD-Ch with low (17 wt%) and medium (25 wt%) cholesterol content exhibited CXCR4 antagonism comparable to unmodified PAMD. Cholesterol modification increased cell uptake of siRNA polyplexes and significantly decreased sensitivity of siRNA transfection to the presence of serum. When used to deliver anticancer siRNA against polo-like kinase 1 (PLK1), polyplexes based on PAMD-Ch with 17 wt% cholesterol exhibited the highest cancer cell killing activity both in serum-free and serum-containing conditions. Overall, the results of this study validate cholesterol modified PAMD as dual-function delivery vectors suitable for efficient delivery of anticancer siRNA and simultaneous CXCR4 inhibition for combined anticancer therapies.

Graphical abstract: Balancing polymer hydrophobicity for ligand presentation and siRNA delivery in dual function CXCR4 inhibiting polyplexes

Article information

Article type
Paper
Submitted
04 Oca 2015
Accepted
23 Şub 2015
First published
11 Mar 2015

Biomater. Sci., 2015,3, 1114-1123

Balancing polymer hydrophobicity for ligand presentation and siRNA delivery in dual function CXCR4 inhibiting polyplexes

Y. Wang, J. Li, Y. Chen and D. Oupický, Biomater. Sci., 2015, 3, 1114 DOI: 10.1039/C5BM00003C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements