Issue 72, 2015

Click synthesis of a polyamidoamine dendrimer-based camptothecin prodrug

Abstract

In the present work we report on the click synthesis of a new camptothecin (CPT) prodrug based on an anionic polyamidoamine (PAMAM) dendrimer intended for cancer therapy. We applied ‘click’ chemistry to improve the polymer-drug coupling reaction efficiency. Specifically, CPT was functionalized with a spacer, 1-azido-3,6,9,12,15-pentaoxaoctadecan-18-oic acid (APO), via a EDC/DMAP coupling reaction. In parallel, propargylamine (PPA) and methoxypoly(ethylene glycol) amine were conjugated to PAMAM dendrimer G4.5 in sequence using an effective coupling agent 4-(4,6-dimethoxy-(1,3,5)triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM). CPT–APO was then coupled to the PEGylated PAMAM dendrimer G4.5–PPA via a click reaction using copper bromide/2,2′-bipyridine/dimethyl sulfoxide (catalyst/ligand/solvent). Human glioma U1242 cells were exposed to the CPT prodrug to determine the toxicity and cell cycle effects using a WST-1 assay and flow cytometry. The CPT prodrug displayed a dose-dependent toxicity with an IC50 of 5 µM, a 185-fold increase relative to free CPT, as a result of slow release. Furthermore, conjugated CPT resulted in G2/M arrest and cell death while the PEGylated dendrimer had little to no toxicity. Altogether, highly efficient click chemistry allows for the synthesis of multifunctional dendrimers for sustained drug delivery.

Graphical abstract: Click synthesis of a polyamidoamine dendrimer-based camptothecin prodrug

Supplementary files

Article information

Article type
Paper
Submitted
30 Apr 2015
Accepted
29 Jun 2015
First published
29 Jun 2015

RSC Adv., 2015,5, 58600-58608

Click synthesis of a polyamidoamine dendrimer-based camptothecin prodrug

O. Yu. Zolotarskaya, L. Xu, K. Valerie and H. Yang, RSC Adv., 2015, 5, 58600 DOI: 10.1039/C5RA07987J

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