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 flexible filaments with spheres of similar chemistry. In rodents, filomicelles persisted in the circulation up to one week after intravenous injection. This is about ten times longer than their spherical counterparts and is more persistent than any known synthetic nanoparticle. Under 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 tumours in mice. Although these findings show that long-circulating vehicles need not be nanospheres, they also lend insight into possible shape effects of natural filamentous viruses.

Polymersomes are self-assembled shells of amphiphilic block copolymers that are currently being developed by many groups for fundamental insights into the nature of self-assembled states as well as for a variety of potential applications. While recent reviews have highlighted distinctive properties - particularly stability - that are strongly influenced by both copolymer type and polymer molecular weight, here we first review some of the more recent developments in computational molecular dynamics (MD) schemes that lend insight into assembly. We then review polymersome loading, in vivo stealthiness, degradation-based disassembly for controlled release, and even tumor-shrinkage in vivo. Comparisons of polymersomes with viral capsids are shown to encompass and inspire many aspects of current designs.

No abstract

Worm-like and spherical micelles are both prepared here from the same amphiphilic diblock copolymer, poly(ethylene oxide)-b-poly (ε-caprolactone) (PEO [5 kDa]-PCL [6.5 kDa]) in order to compare loading and delivery of hydrophobic drugs. Worm-like micelles of this degradable copolymer are nanometers in crosssection and spontaneously assemble to stable lengths of microns, resembling filoviruses in some respects and thus suggesting the moniker "filomicelles". The highly flexible worm-like micelles can also be sonicated to generate kinetically stable spherical micelles composed of the same copolymer. The fission process exploits the finding that the PCL cores are fluid, rather than glassy or crystalline, and core-loading of the hydrophobic anticancer drug delivery, paclitaxel (TAX) shows that the worm-like micelles load and solubilize twice as much drug as spherical micelles. In cytotoxicity tests that compare to the clinically prevalent solubilizer, Cremophor® EL, both micellar carriers are far less toxic, and both types of TAX-loaded micelles also show 5-fold greater anticancer activity on A549 human lung cancer cells. PEO-PCL based worm-like filomicelles appear to be promising pharmaceutical nanocarriers with improved solubilization efficiency and comparable stability to spherical micelles, as well as better safety and efficacy in vitro compared to the prevalent Cremophor® EL TAX formulation. AUTHOR'S PROOFMetadata of the article that will be visualized in OnlineFirst Abstract. Worm-like and spherical micelles are both prepared here from the same amphiphilic diblock 7