Supramolecular "Trojan Horse" for Nuclear Delivery of Dual Anticancer Drugs

J Am Chem Soc. 2017 Mar 1;139(8):2876-2879. doi: 10.1021/jacs.6b12322. Epub 2017 Feb 14.

Abstract

Nuclear delivery and accumulation are very important for many anticancer drugs that interact with DNA or its associated enzymes in the nucleus. However, it is very difficult for neutrally and negatively charged anticancer drugs such as 10-hydroxycamptothecine (HCPT). Here we report a simple strategy to construct supramolecular nanomedicines for nuclear delivery of dual synergistic anticancer drugs. Our strategy utilizes the coassembly of a negatively charged HCPT-peptide amphiphile and the positively charged cisplatin. The resulting nanomaterials behave as the "Trojan Horse" that transported soldiers (anticancer drugs) across the walls of the castle (cell and nucleus membranes). Therefore, they show improved inhibition capacity to cancer cells including the drug resistant cancer cell and promote the synergistic tumor suppression property in vivo. We envision that our strategy of constructing nanomaterials by metal chelation would offer new opportunities to develop nanomedicines for combination chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemistry
  • Camptothecin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Drug Carriers / chemistry
  • Drug Delivery Systems*
  • Drug Screening Assays, Antitumor
  • Humans
  • Macromolecular Substances / chemistry
  • Mice
  • Molecular Structure
  • Nanomedicine
  • Neoplasms / drug therapy*
  • Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • Drug Carriers
  • Macromolecular Substances
  • 10-hydroxycamptothecin
  • Cisplatin
  • Camptothecin