Novel Carbon Nanomaterial Coating for Dispersibility, Delivery and Sensing

Abstract

Carbon nanomaterials have been cited to provide great potential in biomedical applications such as in vivo imaging, drug delivery, and biomarker detection. Yet poor dispersibility in physiological conditions greatly limits their biomedical promise. As with most nanoparticles, the surface interaction with biological systems is the driving force towards effective activity in vivo, namely exhibiting dispersion, low cytotoxicity, and molecular targetability. Therefore, by surface engineering carbon nanomaterials with a distinct biocompatible coating, their applications in imaging, drug delivery, biomarker detection, and therapy can be empowered. We render carbon nanomaterials useful for such in vivo biomedical applications by providing dispersibility, delivery and sensing capabilities with a facile surface coating method. A single, yet multifunctional, hyaluronic acid-based biosurfactant was strategically chosen to meet the design criteria. The amphiphilic material, hyaluronic acid-5Β-cholanic acid (HACA), is an efficient dispersing agent for carbon nanomaterials, including single-walled carbon nanotubes (SWCNTs), in physiological conditions for a sustained period of time. Furthermore, the biological activity and cancer cell targeting of HACA wrapped SWCNTs (HACA-SWCNTs) were evaluated in vitro and in vivo utilizing imaging techniques intrinsic to SWCNTs, HACA, and HACA-SWCNTs. Fluorescent dye-labeled HACA-SWCNTs were designed to activate fluorescence signals intracelluarly, not only serving as an approach to image cellular uptake but also to determine the coating efficacy of HACA onto SWCNTs. SWCNT localization within cells was also confirmed by tracking the intrinsic Raman signals of carbon nanomaterials. In vivo photoacoustic, fluorescence, and positron emission tomography imaging display high tumor targeting capability of HACA-SWCNTs in a murine tumor model. Once targeted, HACA-SWCNTs have potential to serve as photothermal tumor ablation agents after laser activation. HACA coating of carbon nanomaterials creates a system to simultaneously 1) disperse insoluble carbon-based materials, 2) target these coated materials to cancer cells, 3) image intracellular uptake of the platform in vitro and in vivo and, after integrating these properties, 4) serve as therapeutics. This work brings carbon nanomaterials closer to their biomedical potential.