Abstract
Colorectal cancer (CRC) is the fourth most common cancer in the world. Due to its asymptomatic nature, CRC is diagnosed at an advanced stage where the survival rate is <5%. Besides, prognosis from CRC treatment using chemotherapy, radiotherapy and surgery often causes undesirable side-effects. As such, gold nanoparticles (GNPs) are envisaged in the field for the diagnosis and treatment of CRC. GNPs have unique physical, chemical and electrical properties at nanoscale which makes them suitable for application in biomedicine. However, for GNPs to become clinically effective, its internalisation efficiency in the cancer cells must be enhanced. Folate receptor-α (FR) are overexpressed in CRC wherein FR helps in uptake of folic acid within the cell. Tyro3, a novel tyrosine kinase receptor, drives cell proliferation and its overexpression is correlated with poor prognosis in CRC. Their upregulated expression in CRC cells relative to normal cells makes them an ideal target for GNPs using active targeting. Therefore, in this study receptors FR and Tyro3 were simultaneously targeted using specific antibody-coated GNPs in order to enhance uptake and internalisation of GNPs in CRC cells in vitro. Four different types of coated-GNPs were synthesised GNPs-PEG, GNPs-anti-FR, GNPs-anti-Tyro3 and GNPs-anti-(FR+Tyro3) and incubated (0ng – 50ng) with three CRC cell lines including CRL1790, CRL2159 and HCT116. Simultaneous targeting of these receptors by GNPs-anti-(FR+Tyro3) was found to be the most effective in internalisation in CRC cells compared with GNPs targeted singly to FR or Tyro3 (p<0.05). Besides this, results show that Tyro3 mediated similar internalisation efficacy as FR (p<0.05) in CRC using ICP-OES.