RGD-conjugated albumin nanoparticles as a novel delivery vehicle in pancreatic cancer therapy.

Abstract

Integrin αvβ3 receptor is expressed on several types of cancer cells, including pancreatic cancer cells, and plays an important role in tumor growth and metastasis. The ability to target the integrin αvβ3 receptor on cancer cells increases the efficacy of targeted therapy and reduces the side effects. The aim of this study is to develop a novel arginine-glycine-aspartic acid (RGD) peptide -conjugated albumin nanoparticle to enhance the intracellular uptake of anticancer drug into the pancreatic cancer cells through receptor-mediated endocytosis. In the cellular uptake studies, the fluorescent signal of RGD-conjugated BSANPs in BxPC3 cells was higher than that of BSANPs without RGD conjugation as determined by fluorescence spectrophotometer. We also found that BSANPs bound to BxPC3 cells in a time- and concentration-dependent manner. The uptake of RGD-conjugated BSANPs by pancreatic cancer cells was inhibited by an excess amount of free RGD peptide, indicating that the binding and/or uptake were mediated by the αvβ3 receptor. Furthermore, the nanoparticles were found to be located close to the nuclei by using laser scanning confocal microscopy. Besides, no significant in vitro cytotoxicity was observed as measured with MTT assay. Both in vitro and in vivo antitumor efficacy was improved by targeting gemcitabine-loaded nanoparticles to BxPC-3 cells using RGD peptides. Therefore, the RGD-conjugated BSANPs hold great potential as an effective drug delivery system to deliver therapeutic agents to pancreatic cancer.

• Authors: Shunrong Ji, Jin Xu, Bo Zhang, Wantong Yao, Wenyan Xu, Wenzhe Wu, Yongfeng Xu, Hao Wang, Quanxing Ni, Huimin Hou, Xianjun Yu
• Journal: Cancer biology & therapy (Cancer Biol Ther) Vol. 13 Issue 4 Pg. 206-15 (Feb 15 2012) ISSN: 1555-8576 [Electronic] United States
• PMID: 22354009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Albumins
• Oligopeptides
• RGD-albumin conjugate

Topics

• Albumins (administration & dosage)
• Animals
• Cattle
• Cell Line, Tumor
• Drug Delivery Systems
• Microscopy, Confocal
• Microscopy, Fluorescence
• Nanoparticles (administration & dosage)
• Oligopeptides (administration & dosage)
• Pancreatic Neoplasms (drug therapy)