Small interfering RNA delivery by polyethylenimine-functionalised porous silicon nanoparticles

Area of Science:

• Biomaterials Science
• Nanotechnology
• Oncology

Background:

• Glioblastoma exhibits resistance to chemotherapy, partly due to elevated MRP1 gene expression.
• Effective delivery of therapeutic RNA, such as small interfering RNA (siRNA), is crucial for overcoming this resistance.
• Developing safe and efficient nanocarriers for siRNA delivery is a key challenge in cancer therapy.

Purpose of the Study:

• To fabricate and characterize thermally hydrocarbonised porous silicon nanoparticles (THCpSiNPs) for siRNA delivery.
• To evaluate the potential of PEI-coated THCpSiNPs as non-cytotoxic carriers for siRNA in an in vitro glioblastoma model.
• To assess the efficacy of THCpSiNPs in delivering siRNA targeting the MRP1 gene, a marker of glioblastoma chemotherapy resistance.

Main Methods:

• Fabrication of THCpSiNPs and surface functionalization with polyethylenimine (PEI).
• In vitro assessment of siRNA loading, sustained release kinetics, and cellular uptake in glioblastoma cells.
• Quantification of MRP1 mRNA and protein levels following siRNA delivery.
• Evaluation of nanoparticle cytotoxicity and impact on glioblastoma cell proliferation.

Main Results:

• PEI coating on THCpSiNPs enabled sustained siRNA release and enhanced cellular internalisation.
• THCpSiNP-mediated siRNA delivery significantly reduced MRP1 mRNA expression by 63% and MRP1 protein levels by 70%.
• The nanoparticles demonstrated no significant cytotoxicity in glioblastoma cells and markedly reduced cell proliferation.

Conclusions:

• Non-cytotoxic cationic THCpSiNPs are effective carriers for therapeutic siRNA delivery.
• Targeting the MRP1 gene using siRNA delivered by THCpSiNPs can potentially overcome glioblastoma chemotherapy resistance.
• THCpSiNPs represent a promising nanoplatform for developing novel glioblastoma treatment strategies.