Conscripts of the infinite armada: systemic cancer therapy using nanomaterials

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.

Figure 1

50 years of nanomedicine development for cancer. The timeline is not to scale. Abbreviations: AFM, atomic force microscope; CNT, carbon nanotubes; EPR, enhanced permeability and retention; NCI, National Cancer Institute; NP, nanoparticle; PRINT, particle replication in nonwetting templates; SPIO, superparamagnetic iron oxide.

Figure 2

Representation of nanomaterials with comparison to biologics, drawn to scale.

Figure 3

Some proposed steps in the development of a nanomaterial anti-cancer agent. Abbreviations: ADME, absorption, distribution, metabolism and excretion; AFM, atomic force microscope; DLS, dynamic light scattering; EDX, energy dispersive X-ray; IND, investigational new drug application; TEM, transmission electron microscopy.