Issue 11, 2015

Biodegradable glycopolymer-b-poly(ε-caprolactone) block copolymer micelles: versatile construction, tailored lactose functionality, and hepatoma-targeted drug delivery

Abstract

Glycopolymer-b-poly(ε-caprolactone) (GP-PCL) block copolymer micelles (‘glycomicelles’) with tailored lactose functionalities were developed and investigated for hepatoma-targeted doxorubicin (DOX) delivery. Amphiphilic GP-PCL copolymers were readily prepared with controlled lactobionic acid (LBA) functionalities of 20%, 40%, 80%, and 100% (denoted as GP20-PCL, GP40-PCL, GP80-PCL, and GP100-PCL, respectively) through post-polymerization modification of the poly(acryloyl cyclic carbonate)-b-poly(ε-caprolactone) (PAC-b-PCL, 11.6–6.4 kg mol−1) block copolymer with thiolated LBA (LBA-SH) and 2-(2-methoxyethoxy)ethanethiol ((EO)2-SH) via the Michael-type addition reaction. These self-assembled glycomicelles had mean hydrodynamic diameters ranging from 31.9 to 76.8 nm depending on LBA densities, and exhibited high DOX loading efficiencies of 83.0–89.2%. In vitro release studies showed that the DOX release rate depended on the pH and LBA content. Flow cytometric analyses revealed that asialoglycoprotein receptor (ASGP-R) over-expressed HepG2 liver cancer cells following 4 h treatment with DOX-loaded glycomicelles had a 6.6–17.1-fold higher DOX level, depending on LBA densities, as compared to those treated with the corresponding DOX-loaded non-glycomicelles (100% substitution with (EO)2-SH) under otherwise the same conditions. MTT assays demonstrated that DOX-loaded GP20-PCL, GP40-PCL, GP80-PCL and GP100-PCL micelles had much lower half maximal inhibitory concentration (IC50) values of 2.05, 0.75, 0.45 and 0.43 μg DOX equiv. mL−1, respectively, in HepG2 cells than DOX-loaded non-glycomicelles (IC50: 6.55 μg mL−1 DOX equiv. mL−1). Competitive inhibition experiments showed that after the incubation with DOX-loaded glycomicelles for 4 h, more efficient killing activity against free HepG2 cells (−LBA) was observed, as compared to that against LBA-blocked HepG2 cells (+LBA) after a subsequent 72 h incubation. Glycomicelles with tailored LBA functionalities, high drug loading capacity, and high uptake by ASGP-R positive cells are promising candidates for liver cancer chemotherapy.

Graphical abstract: Biodegradable glycopolymer-b-poly(ε-caprolactone) block copolymer micelles: versatile construction, tailored lactose functionality, and hepatoma-targeted drug delivery

Supplementary files

Article information

Article type
Paper
Submitted
26 Nov 2014
Accepted
26 Jan 2015
First published
27 Jan 2015

J. Mater. Chem. B, 2015,3, 2308-2317

Author version available

Biodegradable glycopolymer-b-poly(ε-caprolactone) block copolymer micelles: versatile construction, tailored lactose functionality, and hepatoma-targeted drug delivery

W. Chen, F. Meng, R. Cheng, C. Deng, J. Feijen and Z. Zhong, J. Mater. Chem. B, 2015, 3, 2308 DOI: 10.1039/C4TB01962H

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