title: Genistein-loaded nanoparticles of star-shaped diblock copolymer mannitol-core PLGA-TPGS for the treatment of liver cancer.
abstract: The purpose of this research is to develop nanoparticles (NPs) of star-shaped copolymer mannitol-functionalized PLGA-TPGS for Genistein delivery for liver cancer treatment, and evaluate their therapeutic effects in liver cancer cell line and hepatoma-tumor-bearing nude mice in comparison with the linear PLGA nanoparticles and PLGA-TPGS nanoparticles. The Genistein-loaded M-PLGA-TPGS nanoparticles (MPTN), prepared by a modified nanoprecipitation method, were observed by FESEM and TEM to be near-spherical shape with narrow size distribution. The nanoparticles were further characterized in terms of their size, size distribution, surface charge, drug-loading content, encapsulation efficiency and in vitro drug release profiles. The data showed that the M-PLGA-TPGS nanoparticles were found to be stable, showing almost no change in particle size and surface charge during 3-month storage of their aqueous solution. In vitro Genistein release from the nanoparticles exhibited biphasic pattern with burst release at the initial 4days and sustained release afterwards. The cellular uptake efficiency of fluorescent M-PLGA-TPGS nanoparticles was 1.25-, 1.22-, and 1.29-fold higher than that of the PLGA-TPGS nanoparticles at the nanoparticle concentrations of 100, 250, and 500μg/mL, respectively. In the MPTN group, the ratio of apoptotic cells increased with the drug dose increased, which exhibited dose-dependent effect and a significant difference compared with Genistein solution group (p<0.05). The data also showed that the Genistein-loaded M-PLGA-TPGS nanoparticles have higher antitumor efficacy than that of linear PLGA-TPGS nanoparticles and PLGA nanoparticles in vitro and in vivo. In conclusion, the star-shaped copolymer M-PLGA-TPGS could be used as a potential and promising bioactive material for nanomedicine development for liver cancer treatment.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
authors.forename: Binquan
authors.initials: B
authors.lastname: Wu
authors.affiliation: Clinical Laboratory, The Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, 223002, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: School of Biotechnology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Xie
authors.affiliation: Huainan Laboratory of Clinical Genetics, Huainan First People's Hospital & First Affiliated Hospital, Medical College, Anhui University of Science & Technology, Huainan 232007, China; Stem Cell Engineering Research Center, Anhui University of Science & Technology, Huainan 232001, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shen
authors.affiliation: Huainan Laboratory of Clinical Genetics, Huainan First People's Hospital & First Affiliated Hospital, Medical College, Anhui University of Science & Technology, Huainan 232007, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Huainan Laboratory of Clinical Genetics, Huainan First People's Hospital & First Affiliated Hospital, Medical College, Anhui University of Science & Technology, Huainan 232007, China.
authors.forename: Xinkuang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Huainan Laboratory of Clinical Genetics, Huainan First People's Hospital & First Affiliated Hospital, Medical College, Anhui University of Science & Technology, Huainan 232007, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Stem Cell Engineering Research Center, Anhui University of Science & Technology, Huainan 232001, China.
authors.forename: Fujian
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Stem Cell Engineering Research Center, Anhui University of Science & Technology, Huainan 232001, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Stem Cell Engineering Research Center, Anhui University of Science & Technology, Huainan 232001, China.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Cai
authors.affiliation: Clinical Laboratory, The Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, 223002, China.
authors.forename: De
authors.lastname: Huai
authors.affiliation: Clinical Laboratory, The Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, 223002, China.
authors.forename: Donghui
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Huainan Laboratory of Clinical Genetics, Huainan First People's Hospital & First Affiliated Hospital, Medical College, Anhui University of Science & Technology, Huainan 232007, China.
authors.forename: Rongbo
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Huainan Laboratory of Clinical Genetics, Huainan First People's Hospital & First Affiliated Hospital, Medical College, Anhui University of Science & Technology, Huainan 232007, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory, The Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, 223002, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Huainan Laboratory of Clinical Genetics, Huainan First People's Hospital & First Affiliated Hospital, Medical College, Anhui University of Science & Technology, Huainan 232007, China; Stem Cell Engineering Research Center, Anhui University of Science & Technology, Huainan 232001, China. Electronic address: tangxiaolong_aust@163.com.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Tang
authors.affiliation: Clinical Laboratory, Huai'an First People's Hospital, Nanjing Medical University, Huaian 223003, China. Electronic address: liangyong20142015@163.com.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Sui
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019833:Genistein / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008353:Mannitol / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D004337:Drug Carriers; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008353:Mannitol; D011092:Polyethylene Glycols; D019833:Genistein; C014225:tocophersolan
keywords: Controlled release; Genistein; Liver cancer; Nanomedicine; Star-shaped copolymer