Subcellular-resolution delivery of a cytokine through precisely manipulated nanowires

Abstract

Precise delivery of molecular doses of biologically active chemicals to a pre-specified single cell among many, or a specific sub-cellular location, is still a largely unmet challenge hampering our understanding of cell biology. Overcoming this could allow unprecedented levels of cell manipulation and targeted intervention. Here, we show that gold nanowires conjugated with cytokine, such as tumour necrosis factor-alpha (TNFα), can be transported along any prescribed trajectory or orientation using electrophoretic and dielectrophoretic forces to a specific location with subcellular resolution. The nanowire, 6 μm long and 300 nm in diameter, delivered the cytokine and activated canonical nuclear factor-kappaB signaling in a single cell. Combined computational modeling and experimentation indicated that cell stimulation was highly localized to the nanowire vicinity. This targeted delivery method has profound implications for controlling signaling events on the single cell level.

Ultrahigh-speed rotating nanoelectromechanical system devices assembled from nanoscale building blocks

“…It will also be interesting to exam the release characteristics from multiple nanomotors. In our previous work, we successfully used electric tweezers to deliver drug functionalized nanowires to a single live cell amidst many and characterized responses from the cell 5 , which proved the compatibility of electric tweezers with the actual bioenvironment 5 . Here, the assembling and actuation of nanomotors in a biosetting should be also feasible, as the same ARTICLE electric tweezers technique is used.…”

“…Here, the assembling and actuation of nanomotors in a biosetting should be also feasible, as the same ARTICLE electric tweezers technique is used. We envision the nanomotors as a unique tool for tunable release of biochemicals to a single live cell, which is important for understanding the fundamental signal transduction on single-cell levels 5 . One of the foreseen difficulties is how to position magnetic bearings in the vicinity of selected live cells for assembling nanomotors.…”

“…It has intrigued the research community for over a decade, not only because of the rich fundamental science where devices are made on the nanoscale 1 but also because of the high potential of making technical breakthroughs in various areas including robotics 2 , biomedical research [3][4][5][6] , and optoelectronics 7 .…”

Cell type-dependent uptake, localization, and cytotoxicity of 1.9 nm gold nanoparticles

“…1,2 Few nanostructures have received as much attention as gold nanoparticles, due to the chemically inert nature of gold and the relative ease with which the surface chemistry can be manipulated for downstream applications. [3][4][5][6] Furthermore, gold nanoparticles have been investigated in various contexts in relation to cancer diagnosis and treatment, including as a delivery vehicle for several chemotherapeutic agents, as a contrast agent for enhanced imaging, and for thermal ablation therapy.…”

Electronic properties of nanoentities revealed by electrically driven rotation

“…However, driven motion of suspended nanoentities is well known to be challenging because of the extremely low Reynolds number of 10 −5 where viscous force overwhelms. Nevertheless, it has recently been shown in a scheme termed "electric tweezers" that suspended quasi-1D objects, including CNTs and nanowires, can be compelled to execute translational and rotational motion with precision by DC and AC electric fields applied to patterned electrodes (3)(4)(5)(6). In particular, a suitably administered AC electric field can rotate the suspended 1D entities (7), where the rotation speed, chirality and rotation angle can be precisely controlled by the strength and duration of the applied electric fields.…”