A paclitaxel-conjugated adenovirus vector for targeted drug delivery for tumor therapy.

Abstract

Tumor-targeted drug delivery is an attractive strategy in cancer treatment. Our previous study demonstrated that modified adenovirus has strong tumor targeting ability and less toxicity to surrounding normal tissue. In this study, Paclitaxel (PTX), a widely used clinical anticancer drug, was conjugated to folate-modified adenovirus (Ad) nanoparticles by using succinic anhydride and Fmoc-Glu(OtBu)-OH linkers to form two prodrugs, FA-Ad-Suc-PTX and FA-Ad-ICG02-Glu-PTX. Near-infrared (NIR) fluorescent dye ICG-Der-02 was attached to -NH(2)-Glu(OtBu)-PTX for in vivo optical imaging. In vitro and acute toxicity study demonstrates the low toxicity of the prodrug FA-Ad-Suc-PTX and FA-Ad-ICG02-Glu-PTX compared to the free drug. The dynamic behaviors and targeting ability of FA-Ad-ICG02-Glu-PTX on MDA-MB-231 tumor-bearing mice were investigated by NIR fluorescence imaging. The result show that PTX-conjugated Ad vector could enhance the targeting and residence time in tumor site. In vitro and in vivo studies demonstrate that Coxsackie adenovirus receptor (CAR) or foliate receptor (FR)-mediated uptake of FA-Ad-loaded PTX induced highly anti-tumor activity. The results support the potential of using chemically modified Ad vector as drug-loaded tumor-targeting delivery system.

• Authors: Lingling Shan, Sisi Cui, Changli Du, Shunan Wan, Zhiyu Qian, Samuel Achilefu, Yueqing Gu
• Journal: Biomaterials (Biomaterials) Vol. 33 Issue 1 Pg. 146-62 (Jan 2012) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 21959006 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• CLMP protein, human
• CLMP protein, mouse
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Drug Carriers
• Receptors, Virus
• Paclitaxel

Topics

• Adenoviridae (chemistry)
• Animals
• Antineoplastic Agents (chemistry, therapeutic use)
• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Coxsackie and Adenovirus Receptor-Like Membrane Protein
• Drug Carriers (chemistry)
• Female
• Humans
• Mice
• Mice, Nude
• Nanoparticles (chemistry)
• Neoplasms (drug therapy, metabolism)
• Paclitaxel (chemistry, therapeutic use)
• Receptors, Virus (metabolism)