Editors' ChoiceNanotechnology

Shape Matters Too

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Science Translational Medicine  27 Mar 2013:
Vol. 5, Issue 178, pp. 178ec50
DOI: 10.1126/scitranslmed.3006148

Researchers have been getting creative with antibody-based cancer therapy by focusing more and more on nanoparticles for delivery. As such, the influence of nanoparticle size on site- and cell-specific drug delivery has been well characterized. Now, Barua and colleagues have demonstrated that the nanoparticle’s shape also plays an influential role in the specificity and avidity of antibody-nanoparticle complexes, thus affecting therapeutic efficacy.

Barua et al. found that the therapeutic antibody against Her2, trastuzumab, had increased specificity and avidity to Her2+ breast cancer cells when conjugated to rod- and disk-shaped particles compared with spherical particles and with soluble antibody. This resulted in more cell uptake of antibody-nanorod complexes as well as greater inhibition of Her2+ tumor cell growth compared with albumin-coated nanorods, antibody-nanospheres, and trastuzumab alone. The authors believe that this increased efficacy is likely because rods have a higher surface area per unit volume for antibody binding than spheres. Strikingly, when nanorods were formed from the chemotherapeutic drug camptothecin, trastuzumab-coated camptothecin nanorods achieved equivalent tumor cell growth inhibition at dosages 1000-fold lower than soluble trastuzumab and 10-fold lower than nontargeted camptothecin nanorods.

This study provides quantitative in vitro evidence that shape influences antibody targeting. However, more work is needed to determine whether antibody-nanorod complexes favorably affect tumor cell targeting in vivo, where circulation, immune response, extravasation, and several other factors influence drug delivery. In the near term, this work suggests a translational advantage in using antibody-coated nanorods to increase sensitivity of in vitro diagnostic assays.

S. Barua et al., Particle shape enhances specificity of antibody-displaying nanoparticles. Proc. Natl. Acad. Sci. U.S.A. 110, 3270–3275 (2013). [Abstract]

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