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.
Description
137 pg.
