Unnatural Killer Cells
IMedd (Foster City, CA) is an early-stage biomedical company developing improved drug delivery and medical products based on bioMEMS, microfabrication, and nanotechnology.
The company developed NanoGATE, a small cylindrical implant inserted under the skin providing a continuous alpha interferon release for 36 months.
The implant is designed to maintain drug plasma levels consistently above 50 pg/mL to maintain an antiviral effect but at levels that do not cause acute side effects. Critical to the fabrication of NanoGate implants are NanoPORE membranes, silicon films with parallel rectangular channels arrays from 450 nm in diameter.
Fitted around the implants, 400 microliter reservoirs 12 cm long and 35 cm in diameter capped at both ends, the membranes control diffusion of drugs from the capsule, providing a continuous release of drug for from three to six months.
Frank Martin, Ph.D., IMedd's principal scientist, described NK-Medds (microengineered drug delivery systems), microfabricated porous particles that combine features including targeting, detection, and drug transport and delivery.
IMedd describes these particles as synthetic mini cancer-cell-killing machines that bind to their targets via a specific ligand-receptor interaction, and then release a potent cytolysin into the target cell. NK-Medds consisted of silicon dioxide particles made in the 0.75 m range with pores in the nanometer range.
According to Charles Grove, IMedd president, "These particles are made porous so they are able to act like sponges. We can attach antibodies to them for targeting and fill them with a tumor-cell lytic agent. Currently we use Melittin (bee venom). This substance is released by the particle only upon contact with the target cell."
IMedd has tested NK-Medds particles' ability to specifically kill target cells in vitro. Particles coated with epidermal growth factor (EGF) and loaded with melittin were incubated with either target cells expressing EGF receptors or control cells without the receptor.
Over 95% of the targeted cells were killed, while less than 5% of the control cells were eradicated. "We are at a fairly early stage and need to show antitumor cytolytic activity in animals," Grove notes.
Acute safety studies performed by the company in mice showed that solid, micro-fabricated 5-m disk-shaped particles did not produce acute toxicity at doses of up to one million particles per mouse.