title: Co-delivery of doxorubicin and siRNA for glioma therapy by a brain targeting system: angiopep-2-modified poly(lactic-co-glycolic acid) nanoparticles.
abstract: It is very challenging to treat brain cancer because of the blood-brain barrier (BBB) restricting therapeutic drug or gene to access the brain. In this research project, angiopep-2 (ANG) was used as a brain-targeted peptide for preparing multifunctional ANG-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), which encapsulated both doxorubicin (DOX) and epidermal growth factor receptor (EGFR) siRNA, designated as ANG/PLGA/DOX/siRNA. This system could efficiently deliver DOX and siRNA into U87MG cells leading to significant cell inhibition, apoptosis and EGFR silencing in vitro. It demonstrated that this drug system was capable of penetrating the BBB in vivo, resulting in more drugs accumulation in the brain. The animal study using the brain orthotopic U87MG glioma xenograft model indicated that the ANG-targeted co-delivery of DOX and EGFR siRNA resulted in not only the prolongation of the life span of the glioma-bearing mice but also an obvious cell apoptosis in glioma tissue.
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Lei
authors: L
authors: Wang
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Yongwei
authors: Y
authors: Hao
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Haixia
authors: H
authors: Li
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Yalin
authors: Y
authors: Zhao
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Dehui
authors: D
authors: Meng
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Dong
authors: D
authors: Li
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Jinjin
authors: J
authors: Shi
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Hongling
authors: H
authors: Zhang
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Zhenzhong
authors: Z
authors: Zhang
authors: a School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou , PR China.
authors: Yun
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D004338:Drug Combinations; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: C531860:Angiopep-2; D004338:Drug Combinations; D010455:Peptides; D034741:RNA, Small Interfering; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin
keywords: Blood–brain barrier; DOX; brain delivery; drug delivery; siRNA