轉(zhuǎn)鐵蛋白修飾的BCNU納米材料對C6膠質(zhì)瘤細胞的抗腫瘤及腫瘤靶向作用的體內(nèi)和體外研究.pdf

1、The objective of this study is to evaluate -in vitro and in vivo- thebiocompatibility, antitumor avticity and tumor targeting of Tf-coated BCNU-loadedPoly(D,L-lacticAcid) (PLA) nanoparticles (Tf-BCNU-PLA-NPs) against

2、 C6Glioma cells. The nanoparticles were provided and characteristics were studied bythe College of Material and Engineering of Tianjin University who reported the sizeof NPs as 100～200nm. Our study includes two parts

3、. The first part “In vitro study”: Particiles were prepared with spontaneousemulsification /solvent extraction method. SEM showed that nanoparticles withsmall particle size and narrow size distribution, which had s

4、pherical geometry hadbeen acquired. Bratton-Marshall colorimetric method was used to determine the drugcontent and the influence of initial BCNU content, molecular weight of PLA on drugencapsulation efficiency were ev

5、aluated. The Study of in vitro drug release behaviordemonstrated that BCNU-loaded PLA nanoparticles had shown certain sustainedrelease characteristics. Particles with low molecular weight of PLA showed higherburst eff

6、ect and significantly faster release of drug from PLA samples. The results ofMTT cytotoxicity test significantly demonstrated that drug-loaded nanoparticles hadhigher antitumor activity comparing with free BCNU group,

7、and sustained drugrelease character was achieved as well. In addition, empty nanoparticlesdemonstrated that the matrix had low cytotoxicity and therefore a goodbiocompatibility. For evaluating the tumor targeting

8、of the Tf-coated BCNU-loadedPoly(D,L-lacticAcid) (PLA) nanoparticles (Tf-BCNU-PLA-NPs) in vitro,we usedFluorescent labeling of nanoparticles method, targeting of effect of(Tf-BCNU-PLA-NPs) was observed by Oly

9、mpus phase-contrast fluorescentmicroscopy at defined time intervals and recorded by Olympus microscopy. Resultsshowed that ,after labeling by FITC, the (Tf-BCNU-PLA-NPs) gathered at margin ofglioma cells within 4 hour

10、s detected by fluorescent phase-constract microscopy, thenprofiled the glioma cells at 12 to 24 hours. While the BSA-coated nanoparticles“used as control group” gathered at the margin of C6 glioma cells after 12 hours,

11、 andprofiled glioma cells after 24 hours. The second part ”In vivo study”: For further evaluation of thebiocompatibility, antitumor activity and tumor targeting of the nanoparticles ,the invivo study was

12、 carried out using established intracranial glioma-bearing rats. Theresults demonstrated that (Tf-BCNU-PLA-NPs) had a good biocompatibility , acomparable stronger cytotoxicity by prolonging the mean survival time of ra

13、ts and agood tumor targeting as well, especially when treated at the early time with higherdosage of BCNU, the average survival time of rats treated stereotacticly wasprolonged up to 88.37％, furthermore ,one rat kept

14、normal behavior continuously upto 60 days of observation period. Moreover, another study of different ways of giving(Tf-BCNU-PLA-NPs) to tumor-bearing rats including intracarotid injection andstereotactic and comparin