Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Edited by Joseph M. DeSimone, The University of North Carolina, Chapel Hill, NC, and approved January 10, 2013 (received for review September 27, 2012)
Abstract
Monoclonal antibodies are used in numerous therapeutic and diagnostic applications; however, their efficacy is contingent on specificity and avidity. Here, we show that presentation of antibodies on the surface of nonspherical particles enhances antibody specificity as well as avidity toward their targets. Using spherical, rod-, and disk-shaped polystyrene nano- and microparticles and trastuzumab as the targeting antibody, we studied specific and nonspecific uptake in three breast cancer cell lines: BT-474, SK-BR-3, and MDA-MB-231. Rods exhibited higher specific uptake and lower nonspecific uptake in all cells compared with spheres. This surprising interplay between particle shape and antibodies originates from the unique role of shape in determining binding and unbinding of particles to cell surface. In addition to exhibiting higher binding and internalization, trastuzumab-coated rods also exhibited greater inhibition of BT-474 breast cancer cell growth in vitro to a level that could not be attained by soluble forms of the antibody. The effect of trastuzumab-coated rods on cells was enhanced further by replacing polystyrene particles with pure chemotherapeutic drug nanoparticles of comparable dimensions made from camptothecin. Trastuzumab-coated camptothecin nanoparticles inhibited cell growth at a dose 1,000-fold lower than that required for comparable inhibition of growth using soluble trastuzumab and 10-fold lower than that using BSA-coated camptothecin. These results open unique opportunities for particulate forms of antibodies in therapeutics and diagnostics.
Footnotes
↵1S.B and J.-W.Y. contributed equally to this work.
2Present address: Department of Chemical Engineering, Institute of Chemical Technology, Mumbai 400019, India.
- ↵3To whom correspondence should be addressed. E-mail: samir{at}engineering.ucsb.edu.
Author contributions: S.B., J.-W.Y., P.K., A.W., Y.R.G., and S.M. designed research; S.B., J.-W.Y., and P.K. performed research; S.B., J.-W.Y., A.W., and Y.R.G. contributed new reagents/analytic tools; S.B., J.-W.Y., P.K., A.W., Y.R.G., and S.M. analyzed data; and S.B., J.-W.Y., A.W., Y.R.G., and S.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1216893110/-/DCSupplemental.
Shape-induced enhancement of antibody specificity
Sign up for Article Alerts
Jump to section
You May Also be Interested in
Launched in 1977, Voyagers 1 and 2 are still helping to resolve past controversies even as they help spark a new one: the true shape of the heliosphere.
Image credit: NASA/JPL-Caltech.
Heavy hydrogen makes heavy water more dense and raises its boiling point. It also appears to affect another characteristic long rumored: taste.
Image credit: Shutterstock/sl_photo.
Jonathon Yuly, David Beratan, and Peng Zhang investigate how electron bifurcation reactions work.
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.