Designing Magnetically Responsive Biohybrids Composed of Cord Blood-Derived Natural Killer Cells and Iron Oxide Nanoparticles.

We report the generation of magnetically responsive, cord blood-derived natural killer (NK) cells using iron oxide nanoparticles (IONPs). NK cells are a promising immune cell population for cancer cell therapy as they can target and lyse target tumor cells without prior education. However, NK cells cannot home to disease sites based on antigen recognition, instead relying primarily on external stimuli and chemotactic gradients for transport. Hence, we hypothesized that conjugating IONPs onto the surface of NK cells provides an added feature of magnetic homing to the NK cells, improving their therapeutic function. We describe a robust design for conjugating the IONPs onto the surface of NK cells, which maintains their intrinsic phenotype and function. The conferred magnetic-responsiveness is utilized to improve the cytolytic function of the NK cells for target cells in 2D and 3D models. These findings demonstrate the feasibility of improving NK cell homing and therapeutic efficacy with our NK:IONP "biohybrid".

Rapid Generation and Detection of Biomimetic Oxygen Concentration Gradients In Vitro.

Hypoxic regions exist within most solid tumors and often lead to altered cellular metabolism, metastasis, and drug resistance. Reliable generation and detection of biomimetic gaseous gradients in vitro is challenging due to low spatiotemporal resolution and poor longevity of gradients utilizing microfluidic techniques. Here, we present a novel and simplistic approach for producing gradients of dissolved oxygen (DO) within a lab-on-a-chip platform. Linear and stable DO gradients with high spatial resolution are established by introducing pre-gassed media into the gradient generating network. An underlying platinum(ii) octaethlporphyrin ketone (PtOEPK) based sensor layer allows parallel detection of oxygen. A thin 3-sided glass coating on the inner channel walls prevents multi-directional diffusion of ambient oxygen across PDMS preserving the gradient resolution and stability. Viability analysis of normal mammary epithelial cells (MCF-12A) under oxygen gradients revealed 70% mortality after 6 hours of hypoxic exposure. Biological applicability of the platform was further validated by demonstrating increase in endoplasmic reticulum stress of MDA-MB-468 cells with time and with increasing oxygen tension. The unique ability to establish parallel or opposing gradients of gases and chemicals offers the potential for a wide range of applications in therapeutic development, and fundamental understanding of cellular behavior during hypoxia.