Nanoparticle mediated targeting of VEGFR and cancer stem cells for cancer therapy

Abstract

Angiogenesis is a crucial process in tumor pathogenesis as it sustains malignant cells with nutrients and oxygen. It is well known that tumor cells secrete various growth factors, including VEGF, which triggers endothelial cells to form new capillaries. Prevention of expansion of new blood vessel networks results in reduced tumor size and metastasis. Production of VEGF is driven by hypoxia via transcriptional activation of the VEGF gene by HIF-1α.Tumours are now understood to contain different types of cells, and it is the cancer stem cells that retain the ability to drive the tumour's growth. They are called cancer stem cells because, like stem cells present in normal tissues of the body, they can self-renew and differentiate. These cancer stem cells are responsible for the relapse of cancer as they are found to be resistant to conventional modes of cancer therapy like chemotherapy and radiation.In this review, a novel mode of treatment of cancer is proposed, which utilizes the twin nanoparticle to target endothelial cells in the niche of cancer stem cell. The nanoparticle discussed in this review, is a twin nanoparticle of iron coated with gold, which targets VEGF positive cell in the vicinity of cancer stem cell. In the twin nanoparticle, one particle will recognize cancer stem cell, and another conjugated nanoparticle will recognize VEGF positive cells, thereby inhibiting endothelial cells in the proximity of cancer stem cell. This novel strategy will inhibit angiogenesis near cancer stem cell hence new tumour cannot grow and old tumour will be unable to metastasize.

Figure 1

A pathway regulating tumour growth i.e. cancer stem cells trigger tumour growth in response to hypoxic condition and releases the signal VEGF. The VEGF initiates the endothelial cell to proliferate and form blood vessels to vascularize the growing tumour. As soon as the tumour gets oxygenated, the tumour grows further in size.

Figure 2

The above diagram shows that usually the cancer stem cells gives rise to new tumour in the presence of VEGF or neovascularization in the proximity of cancer stem cells. The novel therapy procedure that targets the endothelial cell in the proximity of cancer stem cell will lead to neither tumour growth nor metastasis.

Figure 3

The above figure demonstrates a twin nanoparticle made of iron oxide and gold which are coupled together along with cancer stem cell marker and VEGF monoclonal antibody. The nanoparticle concentrates on the tumour site using magnet and cancer stem cell marker and then releases VEGF monoclonal antibody so that angiogenesis can be inhibited near cancer stem cell and tumour growth can be stopped.