Nanoparticles for Imaging: Top or Flop?

Abstract

Nanoparticles are frequently suggested as diagnostic agents. However, except for iron oxide nanoparticles, diagnostic nanoparticles have been barely incorporated into clinical use so far. This is predominantly due to difficulties in achieving acceptable pharmacokinetic properties and reproducible particle uniformity as well as to concerns about toxicity, biodegradation, and elimination. Reasonable indications for the clinical utilization of nanoparticles should consider their biologic behavior. For example, many nanoparticles are taken up by macrophages and accumulate in macrophage-rich tissues. Thus, they can be used to provide contrast in liver, spleen, lymph nodes, and inflammatory lesions (eg, atherosclerotic plaques). Furthermore, cells can be efficiently labeled with nanoparticles, enabling the localization of implanted (stem) cells and tissue-engineered grafts as well as in vivo migration studies of cells. The potential of using nanoparticles for molecular imaging is compromised because their pharmacokinetic properties are difficult to control. Ideal targets for nanoparticles are localized on the endothelial luminal surface, whereas targeted nanoparticle delivery to extravascular structures is often limited and difficult to separate from an underlying enhanced permeability and retention (EPR) effect. The majority of clinically used nanoparticle-based drug delivery systems are based on the EPR effect, and, for their more personalized use, imaging markers can be incorporated to monitor biodistribution, target site accumulation, drug release, and treatment efficacy. In conclusion, although nanoparticles are not always the right choice for molecular imaging (because smaller or larger molecules might provide more specific information), there are other diagnostic and theranostic applications for which nanoparticles hold substantial clinical potential.

Tunable and noncytotoxic PET/SPECT-MRI multimodality imaging probes using colloidally stable ligand-free superparamagnetic iron oxide nanoparticles

“…Robust synthesis, uniformity, batch-to-batch reproducibility, scaling-up, and colloidal stability remain aspects to be developed and optimized. 19 The second and most concerning challenge is probe biosafety, in particular their side effects when used in vivo and in clinical applications. Recently, systemic fibrosis was detected in clinical patients who had previously undergone administration of imaging contrast agents for MRI scans.…”

A comparison of immunotoxic effects of nanomedicinal products with regulatory immunotoxicity testing requirements

“…25,26 Depending on the definition used, the number of nanomedicines marketed and under development varies. 10 13 this absence of clinical use of different diagnostic NMPs has been linked to problems of developing NMPs with adequate pharmacokinetic characteristics and reproducible consistency, and considerations on toxicity, biodegradation, and elimination could be other factors. 13 Iron oxide NMPs have been used but are currently no longer on the market.…”

“…10 13 this absence of clinical use of different diagnostic NMPs has been linked to problems of developing NMPs with adequate pharmacokinetic characteristics and reproducible consistency, and considerations on toxicity, biodegradation, and elimination could be other factors. 13 Iron oxide NMPs have been used but are currently no longer on the market. As a different example, Gd 2 O 3 @SiO 2 core-shell NM is an example of an NM under development as a contrast agent for MRI in cancer diagnosis.…”

“…11 Although one of the major benefits claimed for many NMPs is a reduction in unwanted side effects, the use of NMPs does not guarantee the absence of side effects. Systemically available NMPs have the tendency to end up in lymphoid organs, such as the spleen, 12,13 and interactions of NMPs and NM with the immune system play a leading role in the intensity and extent of side effects occurring simultaneously with the therapeutic activity. 14 The immune system is the body's defense against the invasion of foreign material and is also responsible for maintaining the body's homeostasis.…”

Targeted therapeutics in inflammatory atherosclerosis

“…As diagnostic probes, nanoparticles are highly amenable and can be labeled for optical, magnetic resonance imaging (MRI), computed tomography (CT) and nuclear imaging approaches [24,132,133]. In addition, due to the high phagocytic activities of monocytes and macrophages, nanoparticles are suitable for imaging not only inflammatory lesions, but also the dynamics of inflammatory cells in disease [24,134]. Thus, applying nanomedicine at the different stages of monocyte/macrophage dynamics can foster our understanding of inflammation and can be used to modulate these processes.…”