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Cell-specific targeting of nanoparticles by multivalent attachment of small molecules

Nature Biotechnology volume 23, pages 1418–1423 (2005)Cite this article

Abstract

Nanomaterials with precise biological functions have considerable potential for use in biomedical applications. Here we investigate whether multivalent attachment of small molecules can increase specific binding affinity and reveal new biological properties of such nanomaterials. We describe the parallel synthesis of a library comprising 146 nanoparticles decorated with different synthetic small molecules. Using fluorescent magnetic nanoparticles, we rapidly screened the library against different cell lines and discovered a series of nanoparticles with high specificity for endothelial cells, activated human macrophages or pancreatic cancer cells. Hits from the last-mentioned screen were shown to target pancreatic cancer in vivo. The method and described materials could facilitate development of functional nanomaterials for applications such as differentiating cell lines, detecting distinct cellular states and targeting specific cell types.

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Figure 1: Nanoparticle and derived-nanoparticle library.
Figure 2: Heat map representing cellular uptake of different nanoparticle preparations.
Figure 3: Nanoparticle 'hits' identified from the large screen (Fig. 2) were probed against resting and activating macrophages.
Figure 4: Targeting experiments.
Figure 5: In vivo targeting experiments.
Figure 6: In vivo targeting experiments similar to those described in Figure 5 but with different fluorochrome-labeled nanoparticles (same acquisition parameters in each column).

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Acknowledgements

The authors would like to acknowledge the help of Fred Reynolds for synthesizing the CLIO-peptide conjugates, Jan Grimm for radiolabelling, Terry O'Loughlin for molecular modeling and nanoparticle characterization and Jose-Luis Figueiredo, Rabi Upadhyay and Gregory Wojtkiewicz for technical assistance.

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Author notes

  1. Kimberly Kelly and Eric Yi Sun: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Bldg. 149, 13th Street, Room 5403, Charlestown, 02129, Massachusetts, USA

    Ralph Weissleder, Kimberly Kelly, Eric Yi Sun, Timur Shtatland & Lee Josephson

Authors
  1. Ralph Weissleder
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  2. Kimberly Kelly
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  3. Eric Yi Sun
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  5. Lee Josephson
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Corresponding author

Correspondence to Ralph Weissleder.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

List of Compounds Conjugated to Nanoparticles (PDF 212 kb)

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Weissleder, R., Kelly, K., Sun, E. et al. Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol 23, 1418–1423 (2005). https://doi.org/10.1038/nbt1159

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