Friday, February 27, 2015

Graphene Oxide Selectively Targets Cancer Stem Cells

Graphene Oxide Selectively Targets Cancer Stem Cells

A research reported in the journal Oncotarget, provides an insight into the potential efficacy of Graphene Oxide (GO) as a potential new anti-cancer agent, for the selective targeting of cancer stem cells (CSCs).

Introduction

Conventional  cancer treatment, such as chemo-therapy and radiation not very effective against Tumor-initiating cells (TICs), a.k.a. cancer stem cells (CSCs) Hence, these techniques do not eradicate CSCs completely providing an opportunity for  tumor recurrence, metastasis, and/or drug-resistance, which is a significant clinical problem for the effective treatment of cancer. CSCs share many properties with normal stem cells, including immortality and resistance to stress, as well as asymmetric cell division. Under particular cell culture conditions, CSCs proliferate and form 3D-spheroid-like structures, containing CSCs and progenitor cells, which are known as “tumor-spheres” or “onco-spheres”. The CSC population is resistant to DNA-damage, and shows lower levels of ROS production.

Graphene oxide (GO) is the water-soluble derivative of graphene which can be produced with various sizes and bearing varied functional groups and which can be more easily manipulated experimentally, especially in biological systems. Sterile GO dispersions were prepared in a 5% mixture of DMSO in double-distilled water for these studies. Two grades of GO were used, small GO (s-GO) with flake sizes of 0.2 – 2 µm and big GO (b-GO) with flake sizes of 5 – 20 µm, to represent two size classes, where the flakes are either smaller or larger than the target cells.

The main findings are:

1. GO flakes target breast cancer stem cells
2. GO flakes target CSCs, across multiple cancer types
3. GO treatment somehow targets several different signal transduction pathways in cancer cells, to reduce overall “stemness”.
4. GO inhibits mammosphere (3D-tumor-spheres derived from breast cancer cells are also known as mammo-spheres) formation by promoting the differentiation of breast cancer stem cells, supporting our results from the analysis of multiple signal transduction pathways.
5. GO is non-toxic for normal stem cells, and indeed GO promotes their differentiation.

The authors end the article with their vision for future “we envision that GO could be delivered i.v. or p.o., as a new anti-cancer therapeutic, depending on the location of the tumor. Alternatively, GO flakes could also be used as a lavage solution during surgery, to clear the tumor excision site or the peritoneal cavity (as in ovarian or other peritoneal cancers) of residual CSCs, with the aim of preventing tumor recurrence and distant metastasis, via differentiation-based nano-therapy.”

Article citation: Fiorillo, M.; et. al. Graphene oxide selectively targets cancer stem cells, across multiple tumor types: Implications for non-toxic cancer treatment, via “differentiation-based nano-therapy”. Oncotarget, 5. Retrieved from http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=3348&path%5B%5D=6631