Gold nanoparticles mediated drug-gene combinational therapy for breast cancer treatment

Abstract

Background: Cancer is a complex heterogeneous disease to which singular modes of treatment mostly fail to produce a desired therapeutic efficacy. Targeting different cellular pathways using combinational therapies has been gaining popularity in cancer treatment, with the added benefit of reducing dosage and side effects. Methods: A gold nanoparticle-mediated drug delivery nanoplatform was developed for co-delivery of doxorubicin and polo-like kinase 1 (PLK1) siRNA. Gold nanoparticles were coated with polyethyleneimine to facilitate assembly of PLK1 on the surface. Doxorubicin was loaded on nanoparticles through a pH-sensitive linker with a thiol group at one terminal end for controlled release. Results: The therapeutic efficiency of this co-delivery system was evaluated in 2D and 3D cultured systems. The reduced IC50 value clearly demonstrated the synergistic effect of combined drug and gene delivery over their individual delivery in a cancer treatment model. Conclusion: This study may provide an adaptable, facile platform to investigate drug-siRNA combinations for cancer inhibition.