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Suppression of pancreatic tumor growth by targeted arsenic delivery with anti-CD44v6 single chain antibody conjugated nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
6402 489 2013 10 PDF Available
Title
Suppression of pancreatic tumor growth by targeted arsenic delivery with anti-CD44v6 single chain antibody conjugated nanoparticles
Abstract

Arsenic trioxide (As2O3) is a promising anticancer agent for solid tumors. However, the high toxicity to normal tissues resulting from the lack of tumor specificity remains a huge challenge in its systemic application. Targeted vectors enabling drug delivery to specific cancer cells bring about great potential for better therapeutic efficacy whereas low side effects in cancer treatments. Our previous work has demonstrated that the anti-CD44v6 single chain variable fragment (scFvCD44v6) screened out from the human phage-displayed scFv library possesses high specificity and affinity to membrane antigen CD44v6 over-expressing in a subset of epithelium-derived cancers, such as pancreatic, hepatocellular, colorectal and gastric cancers. Herein, a maleimide-functionalized amphiphilic diblock copolymer of poly (ethylene glycol) and poly (d, l-lactide) (mal-PEG-PDLLA) was synthesized and assembled to vesicles with arsenite ion (As) encapsulated in their cores (As-NPs). Conjugation of scFvCD44v6 with mal-PEG-PDLLA (scFv-As-NPs) enabled more efficient delivery of As and exhibited higher cytotoxic activity than non-targeted ones (As-NPs) in human pancreatic cancer cells PANC-1. Furthermore, the targeted delivery of As induced more significant gene suppression in terms of the expression of anti-apoptotic Bcl-2 protein. Consequently, the expression level of cleaved caspase-3 which is a molecular indicator of cell apoptosis was remarkably elevated. In animal tests, scFv-As-NPs were found to greatly increase accumulation of drug in tumor site and potentiate the efficacy of As in inhibiting tumor growth owing to the enhanced cell apoptosis. These results imply that our tumor specific nanocarriers provide a highly efficient and safe platform for pancreatic cancer therapy.

Keywords
Tumor targeting; Arsenic; Nanoparticles; Drug delivery; Pancreatic cancer; CD44v6
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 26, August 2013, Pages 6175–6184
Authors
, , , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us