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Targeting Graphene Quantum Dots to Epidermal Growth Factor Receptor for Delivery of Cisplatin and Cellular Imaging Publisher Pubmed



Nasrollahi F1, 2, 3 ; Koh YR1 ; Chen P1 ; Varshosaz J3 ; Khodadadi AA2 ; Lim S1, 4
Authors
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Authors Affiliations
  1. 1. School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Block N1.3, 637457, Singapore
  2. 2. Catalysis and Nanostructured Materials Laboratory, School of Chemical Engineering, College of Engineering, University of Tehran, P.O. Box: 11155/4563, Tehran, Iran
  3. 3. Novel Drug Delivery Systems Research Centre, Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences and Health Services, Isfahan, 81746-73461, Iran
  4. 4. NTU-Northwestern Institute for Nanomedicine, Nanyang Technological University, 50 Nanyang Drive, Block N3.1, 637553, Singapore

Source: Materials Science and Engineering C Published:2019


Abstract

The unique properties of graphene quantum dots (GQDs) which include high loading capacity, excellent physiological stability, strong photoluminescence, biocompatibility, and facile production make them attractive nanomaterials for biomedical applications. In this work, GQDs have been explored as dual-functional targeted drug carriers and cellular bioimaging agents. The GQDs were conjugated to single chain variable fragment of antibody (scFv), which had been engineered with high affinity (B10) to epidermal growth factor receptor (EGFR), via amide covalent linkages (GQDs-scFvB10). The morphology and surface modification of GQDs were characterized by HRTEM, SDS-PAGE, FT-IR, UV–vis and fluorescence spectroscopies. Western blot analysis along with the confocal imaging of EGFR-overexpressing breast cancer cells (MDA-MB-231) demonstrated the targeting functionality of scFvB10 after conjugation to the GQDs, as well as the potential application of GQDs-scFvB10 in targeted bioimaging. The surface of targeted GQDs had a high cisplatin (CDDP) loading capacity of 50% and a pH-dependent release with slower release rate at neutral conditions, which can reduce the commonly observed systemic toxicity of CDDP. The targeted CDDP-loaded nanocarriers ((CDDP)GQDs-scFvB10) exhibited significantly higher toxicity on MDA-MB-231 cells compared to non-targeted ones suggesting their efficient uptake through EGFR. In contrast, cells with saturated EGFR showed lower uptake and cytotoxic effect of (CDDP)GQDs-scFvB10, demonstrating selectivity of the nanocarriers towards EGFR-overexpressing cells. The scFvB10-functionalized GQD is a promising platform for targeted cellular imaging and delivery of CDDP through interactions with EGFRs. © 2018
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