Nanodiamond-Mediated Delivery of Therapeutics via Particle and Thin Film Architectures

Abstract

Due to their integrative properties that are conducive towards applications in nanomedicine, nanodiamonds (NDs) can serve as highly versatile and biocompatible carbon-based platforms for the controlled functionalization and delivery of a wide spectrum of therapeutic compounds (e.g. small molecule, protein/antibody, nucleic acid, etc.). This chapter explores the development, effectiveness, and potential of drug-functionalized ND materials (2–8 nm in diameter) via particle and thin film architectures for chemotherapeutic delivery. In this study, doxorubicin hydrochloride (Dox), an apoptosis-inducing cytotoxic drug widely used in chemotherapy, as well as Dexamethasone (Dex), a clinically applicable anti-inflammatory were successfully applied toward the functionalization of NDs and introduced towards murine macrophages (e.g. RAW 264.7) and human colorectal carcinoma cells (e.g. HT-29) with preserved cytotoxic efficacy. The adsorption of Dox onto the NDs and its reversible release were achieved by regulating Cl− ion concentration, among other mechanisms and chemical treatment methodologies, and as such, ND particles were found to be able to efficiently ferry the drug inside a broad spectrum of cell lines. Moreover, novel ND thin films were developed by assembling detonation NDs dispersed in aqueous solution into a closely packed ND multilayer nanofilm with positively charged poly-l-lysine (PLL) via the layer by layer (LBL) deposition technique. Comprehensive assays were performed to quantitatively assess and confirm inherent ND biocompatibility in both the particle and thin film architectures via cellular gene expression examination by real time polymerase chain reaction (RT-PCR), DNA fragmentation assays, and mitochondrial function (MTT) analysis, confirming the functional apoptosis-inducing and inflammation-suppressing mechanisms driven by the Dox-functionalized NDs and Dex-functionalized NDs, respectively. The relevance of the Dox–ND composites has been extended toward a translational context, where MTT assays were performed on the HT-29 colon cancer cell line to examine Dox–ND-induced cell death and ND-mediated chemotherapeutic surface sequestering for potential slow- and sustained-release capabilities. Additionally, the functionality of the Dex-ND films was assessed via interrogation of the suppression of inflammatory cytokine release. Suppression of lipopolysaccharide-mediated inflammation was observed through the potent attenuation of tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) levels following ND thin film interfacing with RAW 264.7 murine macrophages. Furthermore, basal cytokine secretion levels examined innate material compati­bility, revealing unchanged quantitative cellular inflammatory responses, which strongly support the non-toxicity and relevance of the NDs as effective treatment platforms for nanoscale medicine. In addition to their straightforward/facile preparation, robustness/resistance to delamination, and fine controllability of the film structures, these hybrid materials possess enormous potential towards biomedical applications such as localized drug delivery and anti-inflammatory implant coatings and devices, as demonstrated in vitro in this chapter.