Shape effects of filaments versus spherical particles in flow and drug delivery.
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.
Geng
Yan
Y
NanoBioPolymers and Molecular & Cell Biophysics Lab, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Dalhaimer
Paul
P
Cai
Shenshen
S
Tsai
Richard
R
Tewari
Manorama
M
Minko
Tamara
T
Discher
Dennis E
DE
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D017022:Flow Injection Analysis / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage*; D010316:Particle Size
D000970:Antineoplastic Agents; D004337:Drug Carriers; D017239:Paclitaxel