title: Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system.
abstract: Chemotherapy for brain cancer tumors remains a big challenge for clinical medicine due to the inability to transport sufficient drug across the blood-brain barrier (BBB) and the poor penetration of drug into the tumors. To effectively treat brain tumors and reduce side effects on normal tissues, both des-octanoyl ghrelin and folate conjugated with polymersomal doxorubicin (GFP-D) was developed in this study to help transport across the BBB and target the tumor as well. The size measurements revealed that this BBB-penetrating cancer cell-targeting GFP-D was about 85 nm. In-vitro experiments with a BBB model and C6 glioma cells demonstrated that GFP-D owned a robust penetrating-targeting function for drug delivery. In C6 cell viability tests, GFP-D exhibited an inhibitory effect significantly different from the unmodified polymersomal doxorubicin (P-D). In-vivo antitumor experiments showed that GFP-D performed a much better anti-glioma effect and presented a significant improvement in the overall survival of the tumor-bearing mice as compared to the treatments with free doxorubicin (Dox), liposomal doxorubicin (L-D), P-D, or single ligand conjugated P-D. In addition, Cy 5.5 was used as a probe to investigate the delivery property of this penetrating-targeting delivery system. The overall experimental results indicate that this BBB-penetrating cancer cell-targeting GFP is a highly potential nanocarrier for the treatment of brain tumors.
authors: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan.
authors: Yung-Chu
authors: YC
authors: Chen
authors: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.
authors: Chi-Feng
authors: CF
authors: Chiang
authors: Divison of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors: Li-Fang
authors: LF
authors: Chen
authors: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.
authors: Po-Chin
authors: PC
authors: Liang
authors: Biomedical Technology and Device Research Labs, Industrial Technology Research Institute, Hsinchu, Taiwan. Electronic address: hsiehw@itri.org.tw.
authors: Wen-Yuan
authors: WY
authors: Hsieh
authors: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; Division of Medical Engineering Research, National Health Research Institutes, Miaoli, Taiwan. Electronic address: winli@ntu.edu.tw.
authors: Win-Li
authors: WL
authors: Lin
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D005492:Folic Acid / Q000737:chemistry*; D054439:Ghrelin / Q000737:chemistry*; D005910:Glioma / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats
chemical_list: D054439:Ghrelin; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005492:Folic Acid
keywords: Blood–brain barrier; Brain tumor; Cancer cell-targeting; Des-octanoyl ghrelin; Folate; Nanomedicine