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Study on the Preparation of RGD-conjugated Albumin Nanoparticles Loaded with Gemcitabine & Its Antitumor Efficacy in BxPC-3 Cell Lines in Vitro and in Vivo

Author: JiShunRong
Tutor: YuXian
School: Fudan University
Course: Surgery
Keywords: Pancreatic cancer Gemcitabine Albumin nanoparticles RGD peptides
CLC: R735.9
Type: Master's thesis
Year: 2011
Downloads: 110
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Abstract


Objective:This study was conducted to prepare RGD-conjugated albumin nanoparticles loaded with gemcitabine and detect their antitumor efficacy to pancreatic cancer cell line BxPC-3 in vitro and in vivo.Methods:①RGD-conjugated albumin nanoparticles were prepared. And their size distribution, drug loading rate and in-vitro drug release rate were detected.②Expression of integrinαvβ3 on the four pancreatic cancer cell lines, BxPC-3, PANC-1, SW1990 and CFPAC-1, were detected.③Uptake of RGD-BSANP by pancreatic cancer cells were detected.④The effect of RGD-BSANP-GEM on cancer cell proliferation and apoptosis were assessed separately with MTT assay and TUNEL method. Its influence on cell cycle was also determined by flow cytometry.⑤The anticancer activity in vivo of RGD-BSANP-GEM was evaluated in BxPC-3 xenografts in nude mice.Results:①RGD-BSANP-GEM with 122nm mean diameter was acquired, and the nanoparticles are well-dispersed, of moderately uniform size distribution, and have smooth surfaces. Drug loading rate is 30.8%; drug release time in-vitro was 8 hours.②BxPC-3 cells have the highest expression of integrinαvβ3 among the four pancreatic cancer cell lines.③RGD-BSANPs bound to BxPC-3 cells in a time- and dose-dependent manner. The uptake of RGD-BSANPs by pancreatic cancer cells was inhibited by an excess amount of free RGD peptides. Furthermore, the nanoparticles were found to locate close to the nuclei by using laser scanning confocal microscopy.④RGD-BSANP-GEM had higher suppressive effect on cancer cell proliferation in vitro compared to BSANP-GEM and GEM.⑤The in vivo experiment also indicated that RGD-BSANP-GEM had obvious inhibitory effect on the growth of the tumor.Conclusions:①RGD peptides can increase the uptake of BSANPs by pancreatic cancer cells.②RGD-BSANP-GEM had good antitumor efficacy in BxPC-3 cell lines both in vitro and in vivo.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Pancreatic tumors
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