Small interfering RNA delivery by polyethylenimine-functionalised porous silicon nanoparticles.
In this study, thermally hydrocarbonised porous silicon nanoparticles (THCpSiNPs) capped with polyethylenimine (PEI) were fabricated, and their potential for small interfering RNA (siRNA) delivery was investigated in an in vitro glioblastoma model. PEI coating following siRNA loading enhanced the sustained release of siRNA, and suppressed burst release effects. The positively-charged surface improved the internalisation of the nanoparticles across the cell membrane. THCpSiNP-mediated siRNA delivery reduced mRNA expression of the MRP1 gene, linked to the resistence of glioblastoma to chemotherapy, by 63% and reduced MRP1-protein levels by 70%. MRP1 siRNA loaded nanoparticles did not induce cytotoxicity in glioblastoma cells, but markedly reduced cell proliferation. In summary, the results demonstrated that non-cytotoxic cationic THCpSiNPs are promising vehicles for therapeutic siRNA delivery.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Mawson Institute, University of South Australia, GPO Box 2471, Adelaide SA 5001, Australia. nico.voelcker@unisa.edu.au.
M
M
Hasanzadeh Kafshgari
M
M
Alnakhli
B
B
Delalat
S
S
Apostolou
F J
FJ
Harding
E
E
Mäkilä
J J
JJ
Salonen
B J
BJ
Kuss
N H
NH
Voelcker
D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000737:chemistry*; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry* / Q000378:metabolism; D016062:Porosity; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D012825:Silicon / Q000737:chemistry*
D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011094:Polyethyleneimine; D034741:RNA, Small Interfering; D012825:Silicon; C421109:multidrug resistance-associated protein 1