Will nanotechnology influence targeted cancer therapy?

Abstract

The rapid development of techniques that enable synthesis (and manipulation) of matter on the nanometer scale and the development of new nanomaterials will play a large role in disease diagnosis and treatment, specifically in targeted cancer therapy. Targeted nanocarriers are an intriguing means to selectively deliver high concentrations of cytotoxic agents or imaging labels directly to the cancer site. Often, solubility issues and an unfavorable biodistribution can result in a suboptimal response of novel agents even though they are very potent. New nanoparticulate formulations allow simultaneous imaging and therapy ("theranostics"), which can provide a realistic means for the clinical implementation of such otherwise suboptimal formulations. In this review, we did not attempt to provide a complete overview of the rapidly enlarging field of nanotechnology in cancer; rather, we presented properties specific to nanoparticles and examples of their uses, which show their importance for targeted cancer therapy.

Figure 1

Patterned array of xenon atoms on a nickel surface (atomic structure not resolved). Each letter is 50 nm from top to bottom. Reprinted with permission from [2].

Figure 2

(A) The principle of multivalency. Antibodies are bivalent while small peptides or small molecules are mono-valent. A particle with multiple targeting moieties provides multiple binding sides and is multivalent. Multivalency increases the validity to the target considerably. (B) A mono-modal imaging agent is suitable to be detected with one modality; a multimodal agent can be detected with several imaging modalities as it contains several different labels. This allows to combine the advantages of various modalities in one particle.

Figure 3

Dispersion of particles as an indicator of the size variability between particles. Monodispersed particles are all uniform and of one size without variability, this is the ideal particle preparation. Oligodispersed particles have some variability in size while polydispersed particles show a large range of sizes. Accordingly, oligo- and polydispersed particles demonstrate different rate of excretions

Figure 4

Schematic representation of advances in magnetic nanoparticle (MNP) design. MNP agents currently under development will have significantly higher relaxivities than earlier generations of MNP, and will also have improved synthetic coats for targeted imaging. The red box indicates an approved agent. The green box indicates the next generation of particles. Reprinted with permission from [30].

Figure 5

CT imaging of a lymph node of a mouse with a bismuth nanoparticle (a,b) Three-dimensional volume renderings of the CT data set, the length of the reconstruction is 3.8 cm. (c) Coronal slice (length of the slice 2.3 cm). (d) Transverse slice at the height indicated by the horizontal lines in b. The maximal diameter of the mouse is 1.8 cm. The position of the lymph node under the right shoulder is indicated by the ovals, and the arrows show the injection site. Note the lack of contrast in the corresponding contralateral (left shoulder) lymph node. Reprinted with permission from [50].

Figure 6

Schematic drawing of the theranostic approach. The diagnostic particle consists of a diagnostic moiety and a coating, modified with a nuclide (green), targeting an antigen (brown), here deposited between the tumor cells. Imaging is performed with MRI and PET. The particle can carry a payload drug (red) that is released in the tumor creating a theranostic agent, allowing for imaging and therapy of the tumor.

Figure 7

Main properties influencing the distribution, elimination and the targeting of particles to tumors. Refer to the main text for details.