Abstract
Aims: Porous silicon nanoparticles (pSiNPs) with tunable pore size are biocompatible and biodegradable, suggesting that they are suitable biomaterials as vehicles for drug delivery. Loading of small interfering RNA (siRNA) into the pores of pSiNPs can protect siRNA from degradation as well as improve the cellular uptake. We aimed to deliver MRP1 siRNA loaded into pSiNPs to glioblastoma cells, and to demonstrate downregulation of MRP1 at the mRNA and protein levels.
Methods: 50-220 nm pSiNPs with an average pore size of 26 nm were prepared, followed by electrostatic adsorption of siRNA into pores. Oligonucleotide loading and release profiles were investigated; MRP1 mRNA and protein expression, cell viability and cell apoptosis were studied.
Results: Approximately 7.7 μg of siRNA was loaded per mg of pSiNPs. Cells readily took up nanoparticles after 30 min incubation. siRNA-loaded pSiNPs were able to effectively downregulate target mRNA (∼40%) and protein expression (31%), and induced cell apoptosis and necrosis (33%).
Conclusion: siRNA loaded pSiNPs downregulated mRNA and protein expression and induced cell death. This novel siRNA delivery system may pave the way towards developing more effective tumor therapies.
| Original language | English |
|---|---|
| Pages (from-to) | 2309-2321 |
| Number of pages | 13 |
| Journal | Nanomedicine |
| Volume | 9 |
| Issue number | 15 |
| DOIs | |
| Publication status | Published - 1 Oct 2014 |
| Externally published | Yes |
Keywords
- drug delivery
- glioblastoma
- MRP1
- porous silicon nanoparticles
- siRNA
- ToF-SIMS
