Efficient co-delivery of a Pt(IV) prodrug and a p53 activator to enhance the anticancer activity of cisplatin

Chem Commun (Camb). 2015 May 7;51(37):7859-62. doi: 10.1039/c4cc09879j.

Abstract

A nanoplatform targeting DNA and p53 simultaneously is assembled. Layered double hydroxide nanoparticles are co-loaded with a Pt(IV) prodrug and a p53 activator. Once inside cells, cisplatin is released to attack genomic DNA and kill cancer cells; simultaneously, the p53 activator results in active p53, a key protein involved in the apoptotic pathways initiated by platinum drugs. The anticancer efficacy of cisplatin is significantly improved through this synergistic application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / administration & dosage
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Mice
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Prodrugs / administration & dosage
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Structure-Activity Relationship
  • Tumor Suppressor Protein p53 / agonists*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Prodrugs
  • Tumor Suppressor Protein p53
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2
  • Cisplatin