Dawn of advanced molecular medicine: nanotechnological advancements in cancer imaging and therapy

Abstract

Nanotechnology plays an increasingly important role not only in our everyday life (with all its benefits and dangers) but also in medicine. Nanoparticles are to date the most intriguing option to deliver high concentrations of agents specifically and directly to cancer cells; therefore, a wide variety of these nanomaterials has been developed and explored. These span the range from simple nanoagents to sophisticated smart devices for drug delivery or imaging. Nanomaterials usually provide a large surface area, allowing for decoration with a large amount of moieties on the surface for either additional functionalities or targeting. Besides using particles solely for imaging purposes, they can also carry as a payload a therapeutic agent. If both are combined within the same particle, a theranostic agent is created. The sophistication of highly developed nanotechnology targeting approaches provides a promising means for many clinical implementations and can provide improved applications for otherwise suboptimal formulations. In this review we will explore nanotechnology both for imaging and therapy to provide a general overview of the field and its impact on cancer imaging and therapy.

FIG. 1

Schematic of nanoparticle for imaging and therapy. Nanoparticles are structures generally described as being less than 100 nm in diameter that can be engineered to display specific chemical, physical, and biological properties. Working in biological environments often necessitates avoidance of the innate and adaptive immune systems often accomplished by polymer or polysaccharide coatings. Targeting of specific sites of disease can be accomplished with targeting moieties, including peptides, antibodies, and aptamers. Nanoparticles provide the opportunity to increase avidity for sites of interest through a strategy of multivalent attachment of a number of targeting ligands. This specific binding to sites of interest can then be exploited by the innate physical or chemical properties of the particle (e.g., quantum dots for fluorescence). Additionally, therapeutic chemicals or radioisotopes may also be conjugated to the particles.

FIG. 2

Schematic representation of the diversity in nanoparticle architecture. A range of chemical and physical production strategies for nanoparticle synthesis results in different classes of particles. (a) Micelles and (b) liposomes are composed of either a single layer or bilayer of lipids, respectively. The interior of these structures can be used to deliver imaging or therapeutic agents. (c) Polymer micelles and (d) polymersomes exploit the same properties of amphipathic molecules, but instead utilize man-made polymers for more stable, but usually larger, structures than liposomes. (e) Metal-based nanoparticles, usually passivated for biological applications with polymer, polysaccharide, or biological surface groups, have been made from an incredible number of different starting materials. Some of the most popular for imaging and therapy are iron oxides, gold, and silver. Carbon-based materials, such as (f) carbon nanotubes and (g) nanodiamonds, are of intense interest because of unique physical properties resulting from these highly structured nanomaterials.

FIG. 3

Construction of a radioluminescent nanocage using silver nanocubes and gold radionuclides. Enhanced tumor uptake was observed after 24 h, based on Cerenkov imaging. Adapted with permission from Ref. . Copyright 2013 American Chemical Society.

FIG. 4

Polymeric nanoparticles in cancer therapy. (a) PLGA nanoparticles delivered meso-tetraphenylporpholactol to prostate cancer xenografts in mice. Treatment of tumors with light resulted in tumor regression due to activation of the phototoxic agent, while the untreated tumors (no light treatment) continued growing. Adapted with permission from Ref. . Copyright 2005 American Chemical Society. (b) Axial contrast-enhanced CT scans of a cholangio-carcinoma patient with lung metastases and coronal images of a tonsillar cancer patient before and after treatment with docetaxel-carrying targeted nanoparticles. Adapted with permission from Ref. . Copyright 2012 American Association for the Advancement of Science. (c) Composite nanomaterials with unique properties, courtesy of their magnetic and radiation-protecting nanoparticle building blocks. Adapted with permission from Ref. . Copyright 2010 American Chemical Society. (d) Intratumoral or intravenous administration of a cytotoxic peptide with polymeric nanoparticles results in tumor regression. Adapted with permission from Ref. . Copyright 2012 American Chemical Society.

FIG. 5

(a) Poly(acrylic acid)-coated iron oxide nanoparticles loaded with Taxol and the fluorophore DiI release their cargo in the presence of esterase and acidic pH. Adapted with permission from Ref. . Copyright 2009 Wiley-VCH Verlag GmbH&Co. (b) In vitro removal of the cucurbit[7] uril cap from cationic gold nanoparticles in the presence of 1-adamatylamine renders them potent cytotoxic agents. Adapted with permission from Ref. . Copyright 2010 Nature Publishing Group. (c) Lysosomal residence of cerium oxide nanoparticles in different cell lines upregulates the nanoparticles’ oxidase activity, (d) leading to enhanced cytotoxicity. Panels (c) and (d) adapted with permission from Ref. . Copyright 2010 American Chemical Society.

FIG. 6

Delivery of a peptide antigen with single-wall carbon nanotubes led to specific immune response toward the antigen in vivo, indicated by the levels of serum IgG that were quantified with ELISA. Adapted with permission from Ref. . Copyright 2011 American Chemical Society.

FIG. 7

(a) Small-molecule-displaying magnetic nanosensors quickly detected up to a single cancer cell in unprocessed blood samples, through changes in the sample’s magnetic resonance signal. Adapted with permission from Ref. . Copyright 2009 American Chemical Society. (b) Detection of cancer biomarkers in clinical fine-needle aspirate samples using a micro-NMR instrument. Adapted with permission from Ref. . Copyright 2011 American Association for the Advancement of Science. (c) Binding magnetic nanodetectors determined the affinity between the cancer biomarker EpCAM and an anti-EpCAM antibody in suspension, as a model platform for investigating dynamic in vivo molecular interactions. Adapted with permission from Ref. . Copyright 2012 Wiley-VCH Verlag GmbH&Co. (d) A nanoparticle-based device monitored the levels of the archetype pro-inflammatory mediator H2O2 through changes in the nanoparticles fluorescence and magnetic signal, using sensory and reporting nanoparticles. Adapted with permission from Ref. . Copyright 2012 Royal Society of Chemistry.