Dataset Information

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line.

ABSTRACT:

Background and objectives

Gemcitabine (Gem) is far from satisfactory as the first-line regimen for pancreatic cancer, and the emergence of albumin nanoparticles offers new hope for the delivery of Gem. In this study, Gem-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully synthesized, characterized, and tested on a BxPC-3 cell line both in vitro and in vivo.

Materials and methods

4-N-myristoyl-gemcitabine (Gem-C14) was obtained first by coupling myristoyl with the 4-amino group of Gem. The Gem-HSA-NPs were then prepared by nanoparticle albumin-bound technology and characterized for particle size, zeta potential, morphology, encapsulation efficiency, drug-loading efficiency, and release characteristics. Using both in vitro and in vivo studies, Gem-C14 and Gem-HSA-NPs were tested on the human pancreatic cancer cell line BxPC-3.

Results

Gem-HSA-NPs showed an average particle size of 150±27 nm, and with an encapsulation rate of 82.99%±3.5% and a drug-loading rate of 10.42%±3.5%, they exhibited a favorable controlled- and sustained-release nature. In in vitro, Gem-C14 was equivalent in cytotoxicity to Gem. In in vivo, the Gem-HSA-NPs exhibited the strongest inhibitory effect on tumor growth but the lowest toxicity among the four groups.

Conclusion

The enhanced in vivo efficacy of Gem-HSA-NPs toward the pancreatic cancer cell line suggests their potential role for use in the clinical field.

SUBMITTER: Yu X

PROVIDER: S-EPMC4636168 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line.

Yu Xinzhe X Di Yang Y Xie Chao C Song Yunlong Y He Hang H Li Hengchao H Pu Xinming X Lu Weiyue W Fu Deliang D Jin Chen C

International journal of nanomedicine 20151030

<h4>Background and objectives</h4>Gemcitabine (Gem) is far from satisfactory as the first-line regimen for pancreatic cancer, and the emergence of albumin nanoparticles offers new hope for the delivery of Gem. In this study, Gem-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully synthesized, characterized, and tested on a BxPC-3 cell line both in vitro and in vivo.<h4>Materials and methods</h4>4-N-myristoyl-gemcitabine (Gem-C14) was obtained first by coupling myristoyl with ...[more]

PMID: 26586944

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Project description:BackgroundTM4SF1 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and affects the development of this cancer. Also, multidrug resistance (MDR) is generally associated with tumor chemoresistance in pancreatic cancer. However, the correlation between TM4SF1 and MDR remains unknown. This research aims to investigate the effect of TM4SF1 on gemcitabine resistance in PDAC and explore the possible molecular mechanism between TM4SF1 and MDR.MethodsThe expression of TM4SF1 was evaluated in pancreatic cancer cell lines and human pancreatic duct epithelial (HPDE) cell lines by quantitative RT-PCR. TM4SF1 siRNA transfection was carried out using Hiperfect transfection reagent to knock down TM4SF1. The transcripts were analyzed by quantitative RT-PCR, RT-PCR and western blotting for further study. The cell proliferation and apoptosis were obtained to investigate the sensitivity to gemcitabine of pancreatic cancer cells after silencing TM4SF1 in vitro. We demonstrated that cell signaling of TM4SF1 mediated chemoresistance in cancer cells by assessing the expression of multidrug resistance (MDR) genes using quantitative RT-PCR. In vivo, we used orthotopic pancreatic tumor models to investigate the effect of proliferation after silencing TM4SF1 by a lentivirus-mediated shRNA in MIA PaCa-2 cell lines.ResultsThe mRNA expression of TM4SF1 was higher in seven pancreatic cancer cell lines than in HPDE cell lines. In three gemcitabine-sensitive cell lines (L3.6pl, BxPC-3, SU86.86), the expression of TM4SF1 was lower than that in four gemcitabine-resistant cell lines (MIA PaCa-2, PANC-1, Hs766T, AsPC-1). We evaluated that TM4SF1 was a putative target for gemcitabine resistance in pancreatic cancer cells. Using AsPC-1, MIA PaCa-2 and PANC-1, we investigated that TM4SF1 silencing affected cell proliferation and increased the percentages of cell apoptosis mediated by treatment with gemcitabine compared with cells which were treated with negative control. This resistance was associated with the expression of multidrug resistance genes including ABCB1 and ABCC1. In vivo, silencing of TM4SF1 in MIA PaCa-2 cell lines increased the effectiveness of gemcitabine-based treatment in orthotopic pancreatic tumor models evaluated using noninvasive bioluminescent imaging.ConclusionThese findings suggest that TM4SF1 is a surface membrane antigen that is highly expressed in pancreatic cancer cells and increases the chemoresistance to gemcitabine. Thus, TM4SF1 may be a promising target to overcome the chemoresistance of pancreatic cancer.

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Dataset Information

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line.

Background and objectives

Materials and methods

Results

Conclusion

Publications

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line.

Similar Datasets

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