Self-assembly regulated anticancer activity of platinum coordinated selenomethionine

Biomaterials. 2018 Mar:157:17-25. doi: 10.1016/j.biomaterials.2017.12.001. Epub 2017 Dec 5.

Abstract

It is urgently desired that self-assembly methods can be used to develop smart nanomedicines with adjustable anticancer activity and concise structure. Herein, we design carrier-free small molecule assemblies of platinum coordinated selenomethionine, which exhibit adjustable anticancer activity regulated by their self-assembly behaviors. The small molecule assemblies are prepared by coordination of selenomethionine esters with cisplatin. Their self-assembly behaviors can be tuned by esterification between selenomethionine and alcohols with different alkyl lengths, which results in adjustable anticancer activities. The coordination assemblies exhibit high anticancer activity as well as low side effects. Mechanistic studies indicate that they can consume glutathione (GSH) and therefore induce high level of reactive oxygen species (ROS) in cancer cells, which further lead to cell apoptosis. Our findings provide new strategies and insights in developing small molecule assemblies for cancer treatment.

Keywords: Anticancer; Coordination; Platinum; Selenium; Self-assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Cisplatin / chemistry
  • Cisplatin / pharmacology*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology*
  • Female
  • Glutathione / metabolism
  • Hep G2 Cells
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Reactive Oxygen Species / metabolism
  • Selenomethionine / chemistry*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Reactive Oxygen Species
  • Selenomethionine
  • Glutathione
  • Cisplatin