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Targeted delivery of etoposide, carmustine and doxorubicin to human glioblastoma cells using methoxy poly(ethylene glycol)‑poly(ε‑caprolactone) nanoparticles conjugated with wheat germ agglutinin and folic acid.
- Source :
-
Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2019 Mar; Vol. 96, pp. 114-128. Date of Electronic Publication: 2018 Nov 04. - Publication Year :
- 2019
-
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.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Cell Line, Tumor
Glioblastoma metabolism
Glioblastoma pathology
Humans
Doxorubicin chemistry
Doxorubicin pharmacology
Drug Delivery Systems methods
Etoposide chemistry
Etoposide pharmacology
Folic Acid chemistry
Folic Acid pharmacology
Glioblastoma drug therapy
Nanoparticles chemistry
Nanoparticles therapeutic use
Polyesters chemistry
Polyesters pharmacology
Polyethylene Glycols chemistry
Polyethylene Glycols pharmacology
Wheat Germ Agglutinins chemistry
Wheat Germ Agglutinins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-0191
- Volume :
- 96
- Database :
- MEDLINE
- Journal :
- Materials science & engineering. C, Materials for biological applications
- Publication Type :
- Academic Journal
- Accession number :
- 30606517
- Full Text :
- https://doi.org/10.1016/j.msec.2018.10.094