These cells remained viable, and with patches containing magnetic nanoparticles the cells could be spatially manipulated using a magnetic field. Since the patches did not completely occlude the cellular surface from the surrounding environment a functional payload could be attached without interfering with the cells ability to perform its native functions. This initial work has led to what is now referred to as Inhibitors,research,lifescience,medical cellular “backpacks”, nanoscale thickness, micrometer-sized, photolithographically patterned heterostructured multilayer systems capable
of noncytotoxically attaching to the membrane of a living cell. It is interesting to note that these “backpacks” can play an integral part in tissue engineering applications, such as in cell aggregate self-assembly [32] which will be discussed briefly Inhibitors,research,lifescience,medical in a later section. To illustrate the use of this concept in a drug delivery scenario, an extension of this technique was exploited as follows. In a recently published study, a method of attaching carefully engineered nanoparticles to the surface of T-cells was identified [7]. Although their application was for a cell therapy approach, the T-cells were used as chaperones for the stimulant drugs. They designed
drug carrying nanoscale vesicles with lipid characteristics for coupling with the sulfur containing molecules on T-cell Tyrphostin AG-1478 supplier surfaces. Inhibitors,research,lifescience,medical In their study the researchers injected these cargo carrying cells, each with approximately 100 vesicles loaded with interleukins IL-15 and IL-21,
into mice with lung and bone marrow tumors. Once reaching the tumors these packets gradually degraded releasing the drugs over a period of one week. Their concept was for the drug molecules being released to reattach to these chaperone Inhibitors,research,lifescience,medical T-cells, stimulating them to replicate and thus provide the Inhibitors,research,lifescience,medical requisite tissue therapy. The techniques proved successful in that within 16 days, all tumors in the mice treated in this fashion disappeared and these mice survived for the entire 100-day experiment. Mice that received no treatment died within 25 days and those that received either T-cells alone or T-cells with injections of interleukins died within 75 days. A few details of their procedure are presented here to stress the relatively straight forward nature of these protocols and instill confidence that the proposed clinical applications can be realized why with a high degree of certainty. Their method exploits the fact that T-cells, like many cell lines, have high levels of reduced thiol groups on their surface, and thus stable coupling of the synthetic drug carrying nanospecies to them is possible. Specifically, liposomes and liposome-like synthetic entities 100–300nm in diameter, with a drug loaded core and phospholipid exterior layer, were linked to the cells via the thiol reactive maleimide head-groups. A simple two-step process achieved the desired conjugation.