• 四川大學(xué)1華西醫(yī)院耳鼻咽喉－頭頸外科;2華西藥學(xué)院;3華西醫(yī)院腫瘤中心,四川成都;

目的:探討PLGA材料構(gòu)建的納米粒載體導(dǎo)入表皮生長因子受體(EGFR)反義寡核苷酸在頭頸鱗癌基因治療中的可行性,為頭頸腫瘤基因治療中載體的選擇提供一個新的研究思路。方法:以PLGA為材料,采用油包水雙乳化溶劑蒸發(fā)法制備載EGFR正義、反義寡核苷酸納米顆粒;納米顆粒轉(zhuǎn)染SCCⅦ細(xì)胞株;MTT法了解納米顆粒對細(xì)胞的毒性;通過實時熒光定量PCR檢測轉(zhuǎn)染后EGFR基因mRNA表達(dá)水平。結(jié)果:獲得了制備載寡核苷酸PLGA納米顆粒工藝流程,PLGA納米顆粒平均粒徑116nm±7.57nm。納米顆粒體外轉(zhuǎn)染SCCⅦ細(xì)胞,MTT結(jié)果顯示納米顆粒對細(xì)胞生長無明顯抑制效應(yīng),同時具有明顯抑制EGFR基因mRNA表達(dá)效應(yīng)。結(jié)論:PLGA納米顆?？梢杂行У剌d入反義寡核苷酸,達(dá)到抑制靶基因的效果,同時無明顯的細(xì)胞毒性。

引用本文： 葉惠平,鄒劍,張懿,趙厚育,楊玉瓊,劉世喜. PLGA納米顆粒作為基因治療載體的實驗研究. 華西醫(yī)學(xué), 2009, 24(8): 2092-2094. doi: 復(fù)制

1. KOHN D B, SADELAIN M, GLORIO S O J C. Occurrence of leukaemia following gene therapy of Xlinked SCID[J]. Nat Rev Cancer,2003,7(3):477-488.
2. FERBER D. Gene therapy: Safer and virusfree?[J] Science,2001,294(5547):1638-1642.
3. LEE K Y, KWON I C, KIM Y H, et al. Preparation of chitosan selfaggregates as a gene delivery system[J]. J Control Release,1998,51(2-3):213-220.
4. PATRA C R, BHATTACHARYA R, WANG E, et al. Targeted delivery of gemcitabine to pancreatic adenocarcinoma using cetuximab as a targeting agent[J]. Cancer Res,2008,68(6):19701978.
5. EL-SAYED I H, HUANG X H, ELSAYED M A. Surface plasmon resonance scattering and absorption of antiEGFR antibody conjugated gold nanoparticles in cancer diagnostics: Applications in oral cancer[J]. Nano Lett,2005,5:829-834.
6. CROMMELIN D J, STORM G, JISKOOT W, et al. Nanotechnological approaches for the delivery of macromolecules[J]. J Contr Rel,2003,87(1-3):81-88.
7. BITTNER B, RONNEBERGER B, ZANGE R, et al. Bovine serum albumin loaded poly(lactide-co-glycolide) microspheres: the influence of polymer purity on particle characteristics[J]. J Microencapsul,1998,15(4):495-514.
8. JOHANSEN P, MEN Y, AUDRAN R, et al. Improving stability and release kinetics of microencapsulated tetanus toxoid by co-encapsulation of additives[J]. Pharm Res,1998,15(7):1103-1110.
9. BALA I, HARIHARAN S, KUMAR M N. PLGA nanoparticles in drug delivery: the state of the art[J]. Crit Rev Ther Drug Carrier Sys,2004,21(5):387-422.
10. SINGH M, BRIONES M, OTT G, et al. Cationicm icroparticles: A potent delivery system for DNA vaccines[J]. Proc Natl Acad Sci U S A,2000,97(2):811-816.
11. BIRNBAUM D T, KOSMALA J D, HENTHORN D B. Controlled release of estradiol from PLGA microparticles: the effect of organic phase solvent on encapsulation and realease[J]. J Control Release,2000,65(3):375-387.
  1. 1. KOHN D B, SADELAIN M, GLORIO S O J C. Occurrence of leukaemia following gene therapy of Xlinked SCID[J]. Nat Rev Cancer,2003,7(3):477-488.
  2. 2. FERBER D. Gene therapy: Safer and virusfree?[J] Science,2001,294(5547):1638-1642.
  3. 3. LEE K Y, KWON I C, KIM Y H, et al. Preparation of chitosan selfaggregates as a gene delivery system[J]. J Control Release,1998,51(2-3):213-220.
  4. 4. PATRA C R, BHATTACHARYA R, WANG E, et al. Targeted delivery of gemcitabine to pancreatic adenocarcinoma using cetuximab as a targeting agent[J]. Cancer Res,2008,68(6):19701978.
  5. 5. EL-SAYED I H, HUANG X H, ELSAYED M A. Surface plasmon resonance scattering and absorption of antiEGFR antibody conjugated gold nanoparticles in cancer diagnostics: Applications in oral cancer[J]. Nano Lett,2005,5:829-834.
  6. 6. CROMMELIN D J, STORM G, JISKOOT W, et al. Nanotechnological approaches for the delivery of macromolecules[J]. J Contr Rel,2003,87(1-3):81-88.
  7. 7. BITTNER B, RONNEBERGER B, ZANGE R, et al. Bovine serum albumin loaded poly(lactide-co-glycolide) microspheres: the influence of polymer purity on particle characteristics[J]. J Microencapsul,1998,15(4):495-514.
  8. 8. JOHANSEN P, MEN Y, AUDRAN R, et al. Improving stability and release kinetics of microencapsulated tetanus toxoid by co-encapsulation of additives[J]. Pharm Res,1998,15(7):1103-1110.
  9. 9. BALA I, HARIHARAN S, KUMAR M N. PLGA nanoparticles in drug delivery: the state of the art[J]. Crit Rev Ther Drug Carrier Sys,2004,21(5):387-422.
  10. 10. SINGH M, BRIONES M, OTT G, et al. Cationicm icroparticles: A potent delivery system for DNA vaccines[J]. Proc Natl Acad Sci U S A,2000,97(2):811-816.
  11. 11. BIRNBAUM D T, KOSMALA J D, HENTHORN D B. Controlled release of estradiol from PLGA microparticles: the effect of organic phase solvent on encapsulation and realease[J]. J Control Release,2000,65(3):375-387.