Investigation of copper-cysteamine nanoparticles as a new photosensitizer for anti-hepatocellular carcinoma

Cancer Biol Ther. 2019;20(6):812-825. doi: 10.1080/15384047.2018.1564568. Epub 2019 Feb 6.

Abstract

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. HCC is now the third leading cause of cancer deaths worldwide, with over 500,000 people affected. However, there is no complete effective (ideal) treatment for liver cancer yet, and the new methods are expected to be discovered. Herein, for the first time, we report the anti-HCC effects of copper-cysteamine nanoparticles (Cu-Cy NPs), a new type of photosensitizers. An in vitro 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows that Cu-Cy NPs could significantly reduce the activity of HepG2 cells at a very low dose after a short time of ultraviolet radiation. In addition, we found that cell death was induced by Cu-Cy NPs, which is associated with cellular apoptosis. This implied that apoptosis might be the main mechanism of the Cu-Cy's anti-HCC activity. Furthermore, we found that Cu-Cy NPs obviously inhibited the tumor growth in vivo. More interestingly, we found that the soluble Cu-Cy NPs were able to enter exosomes which were secreted by tumor cells, and exosomes could be used to deliver Cu-Cy NPs to target tumor cells. All these observations suggest that Cu-Cy NPs have a good potential for cancer treatment.

Keywords: Hepatocellular carcinoma; copper-cysteamine; nanoparticles; photodynamic therapy; photosensitizer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Copper* / chemistry
  • Cysteamine* / chemistry
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Exosomes / metabolism
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Metal Nanoparticles* / chemistry
  • Metal Nanoparticles* / ultrastructure
  • Mice
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Singlet Oxygen / metabolism
  • Solubility
  • Ultraviolet Rays
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Photosensitizing Agents
  • Singlet Oxygen
  • Cysteamine
  • Copper

Grants and funding

This work was supported by the National Natural Science Foundation of China (NSFC) [81760612]; Open Research Project from Key Laboratory of High Incidence Disease Prevent and Control of Guangxi Universities and Colleges [02402214003-1502]; Program of Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, China [GK2015-ZZ01, GKZ201602, GJZ201602]; Innovation Project of Guangxi Graduate Education [30/02407217014C]; Science and Technology Department of Guangxi [AB16380351].