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Shape effects of filaments versus spherical particles in flow and drug delivery

Nature Nanotechnology volume 2, pages 249–255 (2007)Cite this article

Abstract

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.

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Figure 1: Filomicelles and their persistent circulation.
Figure 2: Kinetics of filomicelle length reduction in vivo.
Figure 3: In vitro interactions between filomicelles and phagocytes (P).
Figure 4: Internalization and fragmentation of filomicelles in vitro by human lung-derived epithelial cells.
Figure 5: Filomicelles mediate paclitaxel (TAX) delivery to rapidly growing tumour xenografts on nude mice.

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Acknowledgements

The authors thank S. Goundla for the simulation snapshot of Fig. 1a, and the Bates Laboratory at the University of Minnesota for OE copolymers. This work was funded by NIH grants (DED), Penn's NSF-MRSEC, NTI, and NSEC (NBIC), and Penn's Institute for Translational Medicine and Therapeutics.

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Author notes

  1. Yan Geng and Paul Dalhaimer: These authors contributed equally to this work.

Authors and Affiliations

  1. NanoBioPolymers and Molecular & Cell Biophysics Lab, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Yan Geng, Paul Dalhaimer, Shenshen Cai, Richard Tsai, Manorama Tewari & Dennis E. Discher

  2. Pharmaceutics, Rutgers University, Piscataway, New Jersey, 08854, USA

    Tamara Minko

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  1. Yan Geng
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Correspondence to Yan Geng, Paul Dalhaimer or Dennis E. Discher.

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Geng, Y., Dalhaimer, P., Cai, S. et al. Shape effects of filaments versus spherical particles in flow and drug delivery. Nature Nanotech 2, 249–255 (2007). https://doi.org/10.1038/nnano.2007.70

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