Peptide-functionalized graphene oxide quantum dots as colorectal cancer theranostics

Abstract

Colorectal cancer (CRC) accounts for approximately 10% of all new cancer cases worldwide with significant morbidity and mortality. The current imaging techniques are lacking diagnostic precision while traditional chemotherapeutic strategies are limited by their adverse side effects and poor response in advanced stages. Targeted nanoparticles (NPs) can specifically bind to surface antigens on cancer cells and provide effective delivery of diagnostic and chemotherapeutic agent. Placenta-specific protein 1 (PLAC-1) is overexpressed in CRC and can be used as a target for detection and treatment of the disease. The aim of this work was to develop a targeted nanotheranostic agent for early diagnosis and inhibition of the malignant progression and metastasis of CRC. Graphene oxide quantum dots (QD) were covalently labeled with a peptide (GILGFVFTL) having high affinity to PLAC-1. The covalent coupling between the QD and the peptide was confirmed using a series of physicochemical and morphological characterization techniques. Confocal microscopy was used to evaluate the uptake of QD and QD-P in HCT-29, HT-116 and LS-180 CRC cell lines. Selective targeting of antigen PLAC-1 overexpressed on HT-29 and HCT-116 cells was measured by immunofluorescence. Cell proliferation, cell invasion and extent of PLAC-1 expression in CRC cells after treatment with QD and QD-P were determined. The prepared QD-P showed a significant increase in targeting and specific uptake in cells expressing the antigen PLAC-1 compared to non-functionalized QD. Treatment with QD-P also increased the cell cytotoxicity, reduced the invasiveness of HT-29 and HCT-116 cells by 38% and 62%, respectively, and downregulated the expression of PLAC-1 by 53% and 33%, respectively. These results highlight the potential use of QD-P as a theranostic agent for the detection and treatment of CRC cells expressing the antigen PLAC-1.

Keywords: Colorectal cancer; Peptide targeting; Placenta-specific protein 1; Quantum dots; Theranostics.