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Abstract
Single-walled carbon nanotubes (SWCNTs) can serve as drug delivery/biological imaging agents, as they exhibit intrinsic fluorescence in the near-infrared, allowing for deeper tissue imaging while providing therapeutic transport. In this work, CoMoCAT (Cobalt Molybdenum Catalyst) SWCNTs, chirality-sorted by aqueous two-phase extraction, are utilized for the first time to deliver a drug/gene combination therapy and image each therapeutic component separately via chirality-specific SWCNT fluorescence. Each of (7,5) and (7,6) sorted SWCNTs were non-covalently loaded with their specific payload: the PI3 kinase inhibitor targeting liver fibrosis or CCR5 siRNA targeting inflammatory pathways with the goal of addressing these processes in nonalcoholic steatohepatitis (NASH), ultimately to prevent its progression to hepatocellular carcinoma. PX-866-(7,5) SWCNTs and siRNA-(7,6) SWCNTs were each imaged via characteristic SWCNT emission at 1024/1120 nm in HepG2 and HeLa cells by hyperspectral fluorescence microscopy. Wavelength-resolved imaging verified the intracellular transport of each SWCNT chirality and drug release. The therapeutic efficacy of each formulation was further demonstrated by the dose-dependent cytotoxicity of SWCNT-bound PX-866 and >90% knockdown of CCR5 expression with SWCNT/siRNA transfection. This study verifies the feasibility of utilizing chirality-sorted SWCNTs for the delivery and component-specific imaging of combination therapies, also suggesting a novel nanotherapeutic approach for addressing the progressions of NASH to hepatocellular carcinoma.
Highlights
The use of nanomaterials as gene/drug delivery agents has increased significantly over the past few years, owing to their capability of delivering either water-insoluble or unstable drugs or degradable gene therapeutics
We developed and tested a single-walled carbon nanotube-based drug/gene combination therapeutic platform that allows for the image-tracking of each therapeutic agent
PX-866, targeting inflammation and fibrosis factors that mediate the translation of nonalcoholic steatohepatitis into hepatocellular carcinoma
Summary
The use of nanomaterials as gene/drug delivery agents has increased significantly over the past few years, owing to their capability of delivering either water-insoluble or unstable drugs or degradable gene therapeutics. Single-walled carbon nanotubes (SWCNTs) showed highly promising results for gene/drug delivery coupled with in vitro as well as in vivo imaging [12]. Their quasi-one-dimensional hydrophobic platform aids cellular internalization and the non-covalent or covalent attachment of active agents and Cancers 2019, 11, 1175; doi:10.3390/cancers11081175 www.mdpi.com/journal/cancers. Functionalized with drugs and targeting agents covalently [20] or non-covalently by π-π stacking [13,21], SWCNTs can provide reduced toxicity [22], greater biological activity [16], accumulation in the liver when formulated [10], and controlled drug release [23].
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