The use of myristic acid as a ligand of polyethylenimine/DNA nanoparticles for targeted gene therapy of glioblastoma

摘要

To establish a gene delivery system for brain targeting, a low molecular weight polyethylenimine (PEI_(10K)) was modified with myristic acid (MC), and complexed with DNA, yielding MC-PEI_(10K)/DNA nanoparticles successfully. The nanoparticles were observed to be successfully taken up by the brains of mice. The transfection efficiency of the nanoparticles was then investigated, and both the invitro and invivo gene expression of MC-PEI _(10K)/DNA nanoparticles is significantly higher than that of unmodified PEI_(10K)/DNA nanoparticles. The anti-glioblastoma effect of MC-PEI_(10K)/pORF-hTRAIL was demonstrated by the survival time of intracranial U87 glioblastoma-bearing mice. The median survival time of the MC-PEI_(10K)/pORF-hTRAIL group (28 days) was significantly longer than that of the PEI_(10K)/pORF-hTRAIL group (24 days), the MC-PEI _(10K)/pGL_3 group (21 days) and the saline group (22 days). Therefore, our results suggested that MC-PEI_(10K) could be potentially used for brain-targeted gene delivery and in the treatment of glioblastoma.