Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro

Patel, Nakul ORCID: https://orcid.org/0000-0002-0846-661X, Ghali, Lucy ORCID: https://orcid.org/0000-0003-3410-6615, Roitt, Ivan, Pantoja Munoz, Leonardo ORCID: https://orcid.org/0000-0001-8364-7595 and Bayford, Richard ORCID: https://orcid.org/0000-0001-8863-6385 (2021) Exploiting the efficacy of Tyro3 and folate receptors to enhance the delivery of gold nanoparticles into colorectal cancer cells in vitro. Nanoscale Advances, 3 (18) . pp. 5373-5386. ISSN 2516-0230 [Article] (doi:10.1039/d1na00318f)

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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, 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 the nanoscale which make them suitable for application in biomedicine. However, for GNPs to become clinically effective, their internalisation efficiency in cancer cells must be enhanced. Folate receptor-α (FR) is overexpressed in CRC cells wherein FR helps in the uptake of folic acid within the cells. 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 the 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 (0–50 ng) with three CRC cell lines namely 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 to FR (p <0.05) in CRC cells using ICP-OES.

Item Type: Article
Keywords (uncontrolled): General Engineering, General Materials Science, General Chemistry, Atomic and Molecular Physics, and Optics, Bioengineering
Research Areas: A. > School of Science and Technology > Natural Sciences
Item ID: 33759
Notes on copyright: © 2021 The Author(s). Published by the Royal Society of Chemistry.
This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence
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Depositing User: Jisc Publications Router
Date Deposited: 26 Aug 2021 16:58
Last Modified: 23 Sep 2021 11:20
URI: https://eprints.mdx.ac.uk/id/eprint/33759

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