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Conscripts of the infinite armada: systemic cancer therapy using nanomaterials

Nature Reviews Clinical Oncology volume 7, pages 266–276 (2010)Cite this article

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Abstract

The field of clinical nanomaterials is enlarging steadily, with more than a billion US dollars of funding allocated to research by US government agencies in the past decade. The first generation of anti-cancer agents using novel nanomaterials has successfully entered widespread use. Newer nanomaterials are garnering increasing interest as potential multifunctional therapeutic agents; these drugs are conferred novel properties, by virtue of their size and shape. The new features of these agents could potentially allow increased cancer selectivity, changes in pharmacokinetics, amplification of cytotoxic effects, and simultaneous imaging capabilities. After attachment to cancer target reactive-ligands, which interact with cell-surface antigens or receptors, these new constructs can deliver cytolytic and imaging payloads. The molecules also introduce new challenges for drug development. While nanoscale molecules are of a similar size to proteins, the paradigms for how cells, tissues and organs of the body react to the non-biological materials are not well understood, because most cellular and metabolic processes have evolved to deal with globular, enzyme degradable molecules. We discuss examples of different materials to illustrate interesting principles for development and future applications of these nanomaterial medicines with emphasis on the possible pharmacologic and safety hurdles for accomplishing therapeutic goals.

Key Points

  • Therapeutic uses of novel materials have become widespread; many newer nanoparticles have emerged as candidates for drugs, each with distinctive chemical and biological compositions, and diverse in vivo behaviors

  • Newer nanomaterials are garnering increasing interest as potential multifunctional therapeutic agents, which by virtue of their size, geometric patterning and shape are conferred novel properties

  • The synthesis of nanomaterials allows multifunctional and multivalent molecules to be generated, which may enhance potency, therapeutic index or selectivity

  • The various sizes and shapes of nanomaterials yield very large surface to volume ratios or the possibility of containment for various cargo

  • The accumulation of nanoparticles in tumors, termed the enhanced permeability and retention effect was initially described over two decades ago, and has been successfully applied to nanoparticles

  • The unusual properties of nanomaterials pose challenges to understanding their pharmacokinetics as different components will have different features that affect their distributions, clearance and catabolism

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Figure 1: 50 years of nanomedicine development for cancer.
Figure 2
Figure 3: Some proposed steps in the development of a nanomaterial anti-cancer agent.

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  1. Molecular Pharmacology and Chemistry Program, Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, 10021, NY, USA

    David A. Scheinberg, Carlos H. Villa, Freddy E. Escorcia & Michael R. McDevitt

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  1. David A. Scheinberg
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  2. Carlos H. Villa
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  4. Michael R. McDevitt
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Correspondence to David A. Scheinberg.

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D. A. Scheinberg declares associations with the following company: Encyse Biosciences Inc. M. R. McDevitt declares associations with the following company: Actinium Pharmaceuticals. The other authors declare no competing interests.

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Scheinberg, D., Villa, C., Escorcia, F. et al. Conscripts of the infinite armada: systemic cancer therapy using nanomaterials. Nat Rev Clin Oncol 7, 266–276 (2010). https://doi.org/10.1038/nrclinonc.2010.38

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