Graphene Quantum Dots as Imaging, Sensing, and Targeted Delivery Platform for Cancer Therapeutics

Campbell, Elizabeth

Publication

Graphene Quantum Dots as Imaging, Sensing, and Targeted Delivery Platform for Cancer Therapeutics

Campbell, Elizabeth

Date

7/7/2021

Abstract

The objective of this research is to develop, optimize and test graphene quantum dots (GQDs) as imaging, sensing, and drug delivery platform. GQDs possess properties beneficial for molecular drug delivery/imaging/sensing applications. GQDs exhibit pH-dependent fluorescence in the visible, is water soluble and has a substantial platform for functionalization with multiple therapeutics. GQDs are beneficial for their biocompatibility, small size (< 5 nm), ease in synthesis, and high yield fluorescence in the visible and near-infrared. We explore the imaging and sensing capabilities of GQDs in vitro via their intrinsic fluorescence, pH-dependence of their emission for detection of acidic cancerous environments, and capabilities for in vitro transport of therapeutics. As a result, we expect GQDs to be successful multifunctional agents for imaging, sensing, and drug delivery advancing scientific approach to cancer treatment and therapeutics. This work then develops a new multifunctional biocompatible anticancer nanoformulation to provide targeted image-guided cancer-selective therapeutics. It consists of three active covalently bound components: (1) biocompatible nitrogen-doped graphene quantum dots (GQDs) as a multifunctional delivery and imaging platform, (2) hyaluronic acid (HA) unit targeted to the CD44 receptors on a variety of cancer cells, and (3) oxidative stress-based cancer-selective ferrocene (Fc) therapeutic. The biocompatible GQD platform synthesized from glucosamine exhibits high-yield intrinsic fluorescence. It is utilized for tracking Fc-GQD-HA formulation in vitro indicating internalization enhancement in HeLa cells targeted by the HA over non-cancer HEK-293 cells not overexpressing CD44 receptor. Fc-GQD-HA, non-toxic at 1 mg/mL to HEK-293 cells, induces cytotoxic response in HeLa enhanced over time, while therapeutic ROS generation by Fc-GQD-HA is ~3 times greater than that of Fc alone. This outlines the targeted delivery, imaging, and cancer-specific treatment capabilities of the new Fc-GQD-HA formulation enabling desired cancer-focused nanotherapeutic approach.