Next Article in Journal
Polyphenolic Compositions and Chromatic Characteristics of Bog Bilberry Syrup Wines
Next Article in Special Issue
Introduction to Nanomedicine
Previous Article in Journal
A Click Chemistry Approach towards Flavin-Cyclodextrin Conjugates—Bioinspired Sulfoxidation Catalysts
Previous Article in Special Issue
The Phe-Phe Motif for Peptide Self-Assembly in Nanomedicine
Article Menu

Export Article

Open AccessArticle
Molecules 2015, 20(11), 19849-19864; doi:10.3390/molecules201119664

Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates

1
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic
2
Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53 Prague 2, Czech Republic
3
Department of Hematology, Charles University General Hospital in Prague, U Nemocnice 2, 128 08 Prague 2, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editor: Didier Astruc
Received: 9 September 2015 / Revised: 20 October 2015 / Accepted: 21 October 2015 / Published: 4 November 2015
(This article belongs to the Collection Nanomedicine)
View Full-Text   |   Download PDF [1806 KB, uploaded 4 November 2015]   |  

Abstract

Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW) polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb) rituximab (RTX). The copolymers were linked to the dendrimer core or to the reduced mAb via one-point attachment forming a star-shaped structure with a central antibody or dendrimer surrounded by hydrophilic polymer chains. The anticancer drug doxorubicin (DOX) was attached to the N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer chain in star polymer systems via a pH-labile hydrazone linkage. Such polymer-DOX conjugates were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acidic environments at pH 5–5.5 by hydrolysis of the hydrazone bonds. The cytotoxicity of the polymer conjugates was tested on several CD20-positive or negative human cell lines. Similar levels of in vitro cytotoxicity were observed for all tested polymer conjugates regardless of type or structure. In vivo experiments using primary cell-based murine xenograft models of human diffuse large B-cell lymphoma confirmed the superior anti-lymphoma efficacy of the polymer-bound DOX conjugate when compared with the original drug. Targeting with RTX did not further enhance the anti-lymphoma efficacy relative to the non-targeted star polymer conjugate. Two mechanisms could play roles in these findings: changes in the binding ability to the CD-20 receptor and a significant loss of the immunological properties of RTX in the polymer conjugates. View Full-Text
Keywords: HPMA copolymers; drug delivery systems; doxorubicin; monoclonal antibody; drug targeting HPMA copolymers; drug delivery systems; doxorubicin; monoclonal antibody; drug targeting
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Lidický, O.; Janoušková, O.; Strohalm, J.; Alam, M.; Klener, P.; Etrych, T. Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates. Molecules 2015, 20, 19849-19864.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]

Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top