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

Abstract

These authors contributed equally to this work. Keywords: nanoparticles, albumin, RGD, FITC, delivery, pancreatic cancer, therapyIntegrin avb3 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 avb3 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-glycineaspartic acid (RGD) peptide-conjugated albumin nanoparticle to enhance the intracellular uptake of anticancer drug into the pancreatic cancer cells through receptor-mediated endocytosis. In 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 avb3 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.

Biocompatible and biodegradable fibrinogen microspheres for tumor-targeted doxorubicin delivery

“…14,15 Based on the specific interaction between RGD peptide and α v β 3 integrin, RGD peptide can be extensively conjugated to various drug carriers, showing enhanced cellular uptake by tumor cells. 10,16,17 Therefore, the biocompatibility of Fbg and the RGD sequence present in Fbg may offer a great potential for use in developing biocompatible drug delivery carriers as well as for targeting cancer cells.…”

“…For example, an arginine-glycine-aspartate (RGD) peptide as a tumor-targeting moiety was conjugated onto the albumin nanoparticles with gemcitabine, inhibiting pancreatic tumor cell growth. 10 Furthermore, various targeting molecules, such as folic acid 11 and biotin, 12 have been extensively investigated, demonstrating improved tumor specificity and reduced toxicity to normal cells.…”

Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor

“…To date, there are very few examples of drug-loaded nanoparticles functionalized with specific ligands showing a therapeutic efficacy in experimental pancreatic cancer models. For instance, nanocarriers were decorated with the epidermal growth factor receptor (EGFR) [16], the arginine-glycineaspartic acid (RGD) peptide [17] or an antibody towards the transferrin receptor [18]. However, apart from the fact that these nanodevices exhibited poor drug loading [17,18] they were functionalized with homing devices not specific for pancreatic cancer since typically expressed also on several other types of healthy and/or cancer cells.…”

“…For instance, nanocarriers were decorated with the epidermal growth factor receptor (EGFR) [16], the arginine-glycineaspartic acid (RGD) peptide [17] or an antibody towards the transferrin receptor [18]. However, apart from the fact that these nanodevices exhibited poor drug loading [17,18] they were functionalized with homing devices not specific for pancreatic cancer since typically expressed also on several other types of healthy and/or cancer cells. This explains the inability of these materials to reach the pancreatic cancer tissue, even at a low concentration [19].Therefore, the discovery of more specific ligands for pancreatic tumor targeting is urgently needed and represents an important challenge.…”

1,3-Bis(2-chloroethyl)-1-nitrosourea-loaded bovine serum albumin nanoparticles with dual magnetic resonance–fluorescence imaging for tracking of chemotherapeutic agents

“…26 Briefly, 20 mg of BSA and 1 mg of FITC-BSA were dissolved in 2 mL of sodium chloride solution (10 mM) and stirred for 1 hour. Different concentrations of BCNU were added to the above solution and incubated for another 2 hours before the synthesis of the NPs.…”