X-ray-responsive selenium nanoparticles for enhanced cancer chemo-radiotherapy

Colloids Surf B Biointerfaces. 2016 Mar 1:139:180-9. doi: 10.1016/j.colsurfb.2015.11.063. Epub 2015 Dec 9.

Abstract

Resistance of cancer to radiotherapy and/or chemotherapy is one of the important reasons of clinical treatment failure and recurrence. Chemoradiation is an optional method to over-coming of radioresistance and chemoresistance. Selenium nanoparticles (SeNPs) with special chemical and physical properties, has been identified as a novel nanocarrier and therapy agent with broad-spectrum anticancer activities due to generate ROS in cells. Herein, X-ray responsive selenium nanoparticles were facilely fabricated by using PEG as surface decorator and template. This nanosystem (PEG-SeNPs) demonstrated X-ray responsive property that was attributed to its amorphous characteristic. Interestingly, the nanosystem demonstrated significant radiosensitization effects with X-ray. Specifically, co-treatment of cancer cells with PEG-SeNPs and X-ray significantly and synergistically enhanced the cells growth inhibition through induction of cell apoptosis, as evidenced by DNA fragmentation and activation of caspase-3. In the cell model, we found that internalized nanoparticles could degrade upon X-ray exposure, which further confirm the X-ray responsive property of the nanoparticles. Moreover, the nanosystem could significantly induced intracellular ROS generation in a time-dependent manner, which peaked at about 40min and gradually decreased thereafter. As a results, ROS overproduction led to mitochondria fragmentation and the cell apoptosis. Taken together, this study provides a novel strategy for rational design and facile synthesis of chemo-radio therapeutic radiosensitization nanomaterials.

Keywords: Radiosensitization; Radiotherapy; Selenium nanoparticles; X-ray-responsive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Chemoradiotherapy / methods*
  • DNA Fragmentation / drug effects
  • DNA Fragmentation / radiation effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / radiation effects
  • Gene Expression
  • HeLa Cells
  • Humans
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / pathology
  • Mitochondria / radiation effects
  • NIH 3T3 Cells
  • Nanoparticles / chemistry*
  • Polyethylene Glycols / chemistry
  • Reactive Oxygen Species / agonists
  • Reactive Oxygen Species / metabolism
  • Selenium Compounds / chemistry
  • Selenium Compounds / pharmacology*
  • X-Ray Therapy

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Selenium Compounds
  • Polyethylene Glycols
  • CASP3 protein, human
  • Caspase 3