Gold Nanoparticles Mediated Drug-Gene Combinational Therapy for Breast Cancer Treatment

Int J Nanomedicine. 2020 Oct 21:15:8109-8119. doi: 10.2147/IJN.S258625. eCollection 2020.

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.

Keywords: PLK1; cancer therapy; co-delivery; nanomedicine; pH-responsive.

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / therapy*
  • Cell Cycle Proteins / genetics
  • Combined Modality Therapy
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Carriers / chemistry*
  • Genetic Therapy / methods*
  • Gold / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Metal Nanoparticles / chemistry*
  • Polo-Like Kinase 1
  • Polyethyleneimine / chemistry
  • Protein Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • RNA, Small Interfering / administration & dosage
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / genetics

Substances

  • Antineoplastic Agents
  • Cell Cycle Proteins
  • Drug Carriers
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Gold
  • Doxorubicin
  • Polyethyleneimine
  • Protein Serine-Threonine Kinases