Nanoparticle-based drug delivery: case studies for cancer and cardiovascular applications

Abstract

Nanoparticles (NPs) comprised of nanoengineered complexes are providing new opportunities for enabling targeted delivery of a range of therapeutics and combinations. A range of functionalities can be included within a nanoparticle complex, including surface chemistry that allows attachment of cell-specific ligands for targeted delivery, surface coatings to increase circulation times for enhanced bioavailability, specific materials on the surface or in the nanoparticle core that enable storage of a therapeutic cargo until the target site is reached, and materials sensitive to local or remote actuation cues that allow controlled delivery of therapeutics to the target cells. However, despite the potential benefits of NPs as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of NP materials, as well as their size and shape. The need to validate each NP for safety and efficacy with each therapeutic compound or combination of therapeutics is an enormous challenge, which forces industry to focus mainly on those nanoparticle materials where data on safety and efficacy already exists, i.e., predominantly polymer NPs. However, the enhanced functionality affordable by inclusion of metallic materials as part of nanoengineered particles provides a wealth of new opportunity for innovation and new, more effective, and safer therapeutics for applications such as cancer and cardiovascular diseases, which require selective targeting of the therapeutic to maximize effectiveness while avoiding adverse effects on non-target tissues.

Fig. 1

Computer model of a 30-nm-diameter gold nanoparticle coated with alkanethiol molecules. Nanoparticle gold atoms are shown as yellow spheres, alkyl chain carbon atoms are shown as blue sticks and terminal, and surface-exposed sites are shown as grey spheres. The red background represents the biological environment. The introduction of therapeutic drug molecules (by, e.g., ligand exchange and/or regioselective surface patterning) is depicted by the clusters of molecules terminating in white, orange, and pink spheres to represent different functional groups (D. Thompson, unpublished data)