Dean Ho

The current challenges facing the fields of biological agents and medical therapeutics, such as poor pharmacokinetics and chemoresistance, have necessitated the optimization of therapeutic delivery agents. Among the many platforms being explored, nanodiamonds (NDs) have emerged as promising carriers due to their biocompatibility, scalable synthetic methods, and unique surface-mediated binding of a wide variety of bioactive molecules. ND platforms have also been shown to enhance imaging efficiency, sustain drug release, boost therapeutic efficacy, and improve therapeutic safety profiles. This work addresses recent progress and discusses continued studies toward the potential translation of this unique nanomaterial agent.

Paclitaxel, a potent chemotherapeutic utilized in a variety of cancers, can be limited in its effectiveness due to inherent insolubility in aqueous media and acquired chemoresistance within certain cells. An approach has been developed for increasing Paclitaxel solubility and effectiveness by covalent attachment to gold nanoparticles via DNA linkers. The resulting conjugates are highly soluble in aqueous buffer, exhibiting greater than a 50-fold increase in solubility over the unconjugated drug. DNA linkers are labeled with a fluorophore, which affords a convenient means of visualizing resultant conjugates within cells. Internalized conjugates demonstrate increased activity as compared with free drug across a variety of cell types, including a Paclitaxel-resistant cell line. Attachment to DNA–nanoparticle conjugates may become a general strategy for solubilizing and enhancing a wide variety of therapeutic agents in aqueous media.

Recent reports have revealed that detonation nanodiamonds (NDs) can serve as efficient, biocompatible, and versatile drug delivery platforms. Consequently, further investigations exploring additional therapeutic applications are warranted. Current limitations associated with the non-specific nature of intravenous drugs limit the potential of certain pharmacological agents. One such treatment that could benefit from a stable delivery platform is antibody (Ab) therapy. Determination of Ab adsorption and desorption to a ND surface was subsequently examined using the transforming growth factor β (TGF-β) antibody as a model therapeutic. ND–Ab complexes were found to be stable in water through enzyme-linked immunosorbent assays (ELISAs), UV-vis spectroscopy and TEM, with no Ab released after ten days. Released Abs were detected in extreme pH solutions (3.5), DMEM (+) serum with pH levels ranging from 4 to 10.5, and inorganic saline solutions. Preserved activity of Abs released in DMEM (+) serum was confirmed using an ELISA. These results suggest ND–Ab complexes are synthesized and stabilized in water and are triggered to release active Abs upon exposure to physiological conditions.

Nanodiamond-based drug delivery significantly enhanced treatment efficacy and safety in multiple chemoresistant cancer models.

Cells represent the basic units of life and contain an intertwined network of signaling and regulatory circuitries that drive the processes of life. These processes include the mediation of mechano-sensation, onset of and protection against disease, inflammation, and others. In the network of bio-complex systems, each pathway interacts nonlinearly with others through different molecular intermediates. As a result, specific functionalities can not be simply linked to the cellular molecules in isolation. A complex system generally possesses very rich information content that can be characterized by the following features: (i) they contain a large number of building blocks; (ii) their interactions among building blocks and with their environment; (iii) they display organization without an external organizing principle being applied; and (iv) they exhibit adaptability and robustness. These properties account for the innate intelligence of biology and its ability to regulate its homeostatic behavior. However, this same complexity underlies, in cancer for example, challenges towards disease management, as the addressing of singular pathways with therapeutic compounds is not sufficient. Therefore, combinatorial therapy often serves as a key strategy towards tumor suppression. Because iterative searching for optimized therapeutic combinations is indeed a daunting, if not preclusive task, we introduce the feedback system control (FSC) scheme, which may serve as a clinically relevant approach, provided a translational approach towards drug delivery is employed. Due to their innate biocompatibility, which has been comprehensively observed, as well as their ability to delivery virtually any type of therapeutic in a sustained fashion due to their unique surface properties, nanodiamonds may serve as a foundation for nano-enabled combinatorial therapy.

A paper by Treussart and co-workers in this issue demonstrates the application of photoluminescent nanodiamonds for intracellular labeling as well as mechanistic cellular uptake studies. Findings from this paper reveal that optimal photoluminescence of nitrogen-vacancy color centers can be attained with photostability and no photoblinking, enabling continuous tracking in the cytoplasm over sustained time scales. In addition to the fluorescent properties of the nanodiamonds, internalization assays reveal a primarily endocytic uptake process. A high degree of nanodiamond (∼46 nm in diameter) and endosome colocalization as well as cytoplasmic presence of smaller nanodiamonds was observed. Several attributes of the nanodiamond particles are elucidated in this and other recent studies, ranging from their stability as imaging agents to their potential as intracellular molecular delivery vehicles. These findings give insight into the use of nanodiamonds as an emerging platform for therapeutic and diagnostic (“theranostic”) nanomedicine, forging new foundations and criteria for continued nanodiamond engineering toward downstream clinical relevance and impact.