ABSTRACT
BACKGROUND: fluorescent nanodiamonds (FND) are nontoxic, infinitely photostable nanoparticles that emit near-infrared fluorescence and have a modifiable surface allowing for the generation of protein-FND conjugates. FND-mediated immune cell targeting may serve as a strategy to visualize immune cells and promote immune cell activation. METHODS: uncoated-FND (uFND) were fabricated, coated with glycidol (gFND), and conjugated with immunoglobulin G (IgG-gFND). In vitro studies were performed using a breast cancer/natural killer/monocyte co-culture system, and in vivo studies were performed using a breast cancer mouse model. RESULTS: in vitro studies demonstrated the targeted immune cell uptake of IgG-gFND, resulting in significant immune cell activation and no compromise in immune cell viability. IgG-gFND remained at the tumor site following intratumoral injection compared to uFND which migrated to the liver and kidneys. CONCLUSION: antibody-conjugated FND may serve as immune drug delivery vehicles with "track and trace capabilities" to promote directed antitumor activity and minimize systemic toxicities.
ABSTRACT
Fluorescent nanodiamonds (FNDs) are nontoxic, infinitely photostable, and emit fluorescence in the near infrared region. Natural killer (NK) cells and monocytes are part of the innate immune system and are crucial to the control of carcinogenesis. FND-mediated stimulation of these cells may serve as a strategy to enhance anti-tumor activity. FNDs were fabricated with a diameter of 70±28 nm. Innate immune cell FND uptake, viability, surface marker expression, and cytokine production were evaluated in vitro. Evaluation of fluorescence emission from the FNDs was conducted in an animal model. In vitro results demonstrated that treatment of immune cells with FNDs resulted in significant dose-dependent FND uptake, no compromise in cell viability, and immune cell activation. FNDs were visualized in an animal model. Hence, FNDs may serve as novel agents with "track and trace" capabilities to stimulate innate immune cell anti-tumor responses, especially as FNDs are amenable to surface-conjugation with immunomodulatory molecules.
