Engineering functionalized diamond nanoparticles for intracellular delivery of nucleic acids

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The objective of my research program is to engineer novel nanomaterials that carry nucleic acids into mammalian cells. Gene delivery has been a significant research area of interest for the past two decades, but the mainstream chemical gene delivery nanomaterials, lipids and polymers pose limitations with respect to their stability, efficiency and toxicity. My research program focuses on the use of solid-core nanoparticles, such as nanodiamonds, to overcome these barriers. Nanodiamonds have advantages over lipid and polymer nanoparticles by virtue of a uniform size distribution and a large surface area available for chemical modifications. They are nontoxic in doses necessary for gene delivery.****My research strategy is to chemically link amino acids to the nanodiamond in order to facilitate their interaction with nucleic acids. The novelty of this program lies in the approaches to the synthesis of nanoparticles conjugated with bioactive molecules, amino acids.****The short-term research objectives build on my previous work: design of self-assembling lipid-based and diamond-based nanoparticles. To achieve our goal, we will chemically link amino acids on the surface of the nanodiamond resulting in functionalized nanoparticles with surface properties amenable to binding nucleic acids. We will assess the ability of these functionalized nanoparticles to deliver the bound nucleic acids into model mammalian cells. The pathways of cellular uptake and the mechanism of potential toxicity will be investigated. Relationships between structure/architecture - delivery efficiency/toxicity will be established. This will lead to the identification of candidate vectors with optimal properties (improved binding properties, stability, and cellular uptake with no or minimal toxicity) for delivering nucleic acids into cells.****To study the architecture of the delivery systems, high-resolution microscopy, flow cytometry and synchrotron-based techniques will be used. Correlating the surface properties of these nanoparticles with the delivery efficiency will allow for mapping universal and carrier-specific delivery mechanisms.****On the long term, we will explore whether the basic knowledge on chemical functionalization of the nanodiamond particles could be expanded to other solid-core and soft nanoparticles, establishing universal delivery principles for nucleic acids. This research program will advance knowledge of the use and safety of the functionalized diamond-core nanoparticles as delivery systems for nucleic acids. Optimization of the characteristics of these delivery systems will benefit nanotechnology drug delivery (a global market of $1.2 billion with an estimated growth rate of 49% in the next decade), eventually leading to gene therapy in humans and animals. Understanding the interactions of nanodiamonds with nucleic acids can also translate into biosensor applications.******