Abstract |
Wheat germ agglutinin (WGA) and folic acid (FA)-grafted methoxy poly( ethylene glycol) ( MPEG)‑poly(ε‑caprolactone) (PCL) nanoparticles (WFNPs) were applied to transport anticancer drugs across the blood-brain barrier and treat glioblastoma multiforme (GBM). PCL was copolymerized with MPEG, and MPEG-PCL NPs were stabilized with pluronic F127 using a microemulsion- solvent evaporation technique and crosslinked with WGA and FA. The targeting ability of WFNPs loaded with etoposide (ETO), carmustine ( BCNU) and doxorubicin (DOX) was investigated via the binding affinity of drug-loaded NP formulations to N‑acetylglucosamine expressed in human brain microvascular endothelial cells and to folate receptor in malignant U87MG cells. We found that a shorter PCL chain in drug-loaded MPEG-PCL NPs yielded a smaller average size of the particles. An increase in PCL chain length (stronger hydrophobicity) enhanced drug entrapment efficiencies in MPEG-PCL NPs, and reduced drug-releasing rates from NP formulations. In addition, anti-proliferative activity against U87MG cells for the 3 drugs followed the order of WFNPs > FA-grafted NPs > WGA-grafted NPs > MPEG-PCL NPs. Immunofluorescence staining revealed that the ligands of drug-loaded WFNPs connected to N‑acetylglucosamine and folate receptor with the help of surface WGA and FA. WFNPs carrying ETO, BCNU and DOX acted as dual-targeting nanocarriers, and their use can be a promising approach to inhibiting GBM growth in the brain.
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Authors | Yung-Chih Kuo, Yu-Hsuan Chang, Rajendiran Rajesh |
Journal | Materials science & engineering. C, Materials for biological applications
(Mater Sci Eng C Mater Biol Appl)
Vol. 96
Pg. 114-128
(Mar 2019)
ISSN: 1873-0191 [Electronic] Netherlands |
PMID | 30606517
(Publication Type: Journal Article)
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Copyright | Copyright © 2018 Elsevier B.V. All rights reserved. |
Chemical References |
- Polyesters
- Wheat Germ Agglutinins
- polycaprolactone
- Polyethylene Glycols
- Etoposide
- Doxorubicin
- Folic Acid
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Topics |
- Cell Line, Tumor
- Doxorubicin
(chemistry, pharmacology)
- Drug Delivery Systems
(methods)
- Etoposide
(chemistry, pharmacology)
- Folic Acid
(chemistry, pharmacology)
- Glioblastoma
(drug therapy, metabolism, pathology)
- Humans
- Nanoparticles
(chemistry, therapeutic use)
- Polyesters
(chemistry, pharmacology)
- Polyethylene Glycols
(chemistry, pharmacology)
- Wheat Germ Agglutinins
(chemistry, pharmacology)
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