Biocompatible co-loading vehicles for delivering both nanoplatin cores and siRNA to treat hepatocellular carcinoma

Int J Pharm. 2019 Dec 15:572:118769. doi: 10.1016/j.ijpharm.2019.118769. Epub 2019 Oct 26.

Abstract

Bmi-1 is a gene related to malignant transformation in hepatocellular carcinoma (HCC). The liver cancer cells developed the ability to tolerate CDDP treatment with the elevation of Bmi-1. Bmi-1 is also an oncogene promoting malignance of tumor and an anti-cancer target in many studies. Herein, a biocompatible nanocarrier was designed in the study to deliver a chemotherapeutical agent CDDP and Bmi-1 siRNA to kill cancer cells and silence drug resistance related gene simultaneously. Calciumphosphate (CaP) was applied to coat both nanoplatin cores and siRNA as a shell for the purpose of delivering cargos to the cytosol of the tumor cells. Nanoplatin and siRNA co-loaded CaP nanoparticles (NPSC) enhanced cell uptake of CDDP and showed elevated drug accumulation in tumor. NPSC achieved considerable anti-cancer efficacy and counter-regulated drug tolerance, therefore, warranted a further investigation as a novel therapeutic nanosystem to improve cancer therapy.

Keywords: Bmi-1; Calcium phosphate nanoparticles; Combination therapy; Nanoplatin; siRNA.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Biocompatible Materials / chemistry*
  • Calcium Phosphates / chemistry
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Polycomb Repressive Complex 1 / genetics
  • RNA, Small Interfering / chemistry*

Substances

  • Antineoplastic Agents
  • Biocompatible Materials
  • Calcium Phosphates
  • RNA, Small Interfering
  • calcium phosphate
  • Polycomb Repressive Complex 1