期刊
ONCOLOGY REPORTS
卷 27, 期 1, 页码 121-128出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2011.1459
关键词
glioma; nanoparticles; transferrin; poly(D,L-lactic acid); wafer; BCNU
类别
资金
- National Natural Science Foundation of China [30971136, 51073118, 81001128, 51103107]
- Program for New Century Excellent Talents in University [NCET-08-0393]
The objective of this study was to develop a combination chemotherapy of implantation of a 3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-loaded wafer and intracarotid perfusion of BCNU-loaded nanoparticles for glioma treatment in vivo. BCNU-loaded poly(D,L-lactic acid) (PLA) nanoparticles coated with transferrin (Tf) were prepared by a solvent evaporation/diffusion method using Tf as the emulsifier. X-ray photoelectron spectroscopy, Bratton-Marshall colorimetric assay and zeta-potential analysis confirmed the existence of Tf on the nanoparticles and their functional activities. BCNU-loaded PLA wafers were made of BCNU-loaded PLA microspheres. In vitro drug release behavior demonstrated that BCNU was released from the Tf-PLA nanoparticles and wafers in two distinct phases. The biodistribution of Tf-coated nanoparticles investigated by (99m)Tc-labeled single-photon emission computed tomography (SPECT) showed that the surface-containing Tf-PLA nanoparticles were concentrated in the brain. Inhibition of tumor growth in the C6 glioma-bearing animal model showed that combinational chemotherapy of BCNU-loaded wafer and BCNU-loaded PLA nanoparticles had a stronger inhibitory effect and prolonged the average survival time of rats (164%) compared with that of the control group. Furthermore, the tumors of this treatment group were not visible by examination at 4 weeks. The results of this study demonstrate for the first time that combination therapy of implantation of a BCNU-loaded wafer and intracarotid perfusion of BCNU-loaded nanoparticles may be a new strategy for glioma gene therapy.
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