SOFT FILAMENTS CIRCULATE LONGER THAN SPHERICAL PARTICLES - SHAPE EFFECTS IN FLOW AND DRUG DELIVERY

摘要

Interaction of spherical particles with cells and within animals has been studied extensively, but the effects of shape have received little attention. Here we use highly stable, polymer micelle assemblies known as 'filomicelles' to compare the transport and trafficking of these flexible filaments to spheres of similar chemistry. In rodents, filomicelles persisted in the circulation up to 1 week after intravenous injection. This is about ten-fold longer than their spherical counterparts and more persistent than any known synthetic nanoparticle. With cells and in fluid flow conditions, spheres and short filomicelles are taken up by cells more readily than longer filaments because the latter are extended by the flow. Preliminary results further demonstrate that filomicelles can effectively deliver the anticancer drug paclitaxel and shrink human-derived tumors in mice. These findings redefine what is 'nano' for circulating vehicles and perhaps also lend insight into shape advantages of natural filoviruses.