Polymersomes conjugated with des-octanoyl ghrelin and folate as a BBB-penetrating cancer cell-targeting delivery system
Journal
Biomaterials
Journal Volume
35
Journal Issue
13
Pages
4066-4081
Date Issued
2014
Author(s)
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 85nm. 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, Cy5.5 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. ? 2014 Elsevier Ltd.
SDGs
Other Subjects
Blood-brain barrier; Brain tumors; Cancer cell-targeting; Folate; Ghrelin; Blood; Brain; Cells; Chemotherapy; Drug delivery; Experiments; Medical nanotechnology; Polymers; Tumors; des octanoyl ghrelin folate polymersomal doxorubicin; doxorubicin; folic acid; ghrelin; unclassified drug; doxorubicin; folic acid; ghrelin; macrogol derivative; animal experiment; animal model; antineoplastic activity; article; blood brain barrier; brain tumor; cancer cell; cell viability; controlled study; cytotoxicity; drug conjugation; drug delivery system; drug penetration; drug transport; glioma cell; male; mouse; nonhuman; overall survival; priority journal; rat; therapy effect; analogs and derivatives; animal; Bagg albino mouse; blood brain barrier; chemistry; drug delivery system; glioma; metabolism; nude mouse; procedures; tumor cell line; Mus; Animals; Blood-Brain Barrier; Cell Line, Tumor; Doxorubicin; Drug Delivery Systems; Folic Acid; Ghrelin; Glioma; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Polyethylene Glycols; Rats
Type
journal article