Near-infrared fluorescent nanoprobes for cancer molecular imaging: status and challenges

doi:10.1016/j.molmed.2010.08.006

Trends in Molecular Medicine

Volume 16, Issue 12, December 2010, Pages 574-583

https://doi.org/10.1016/j.molmed.2010.08.006 Get rights and content

Near-infrared fluorescence (NIRF) imaging promises to improve cancer imaging and management; advances in nanomaterials allow scientists to combine new nanoparticles with NIRF imaging techniques, thereby fulfilling this promise. Here, we present a synopsis of current developments in NIRF nanoprobes, their use in imaging small living subjects, their pharmacokinetics and toxicity, and finally their integration into multimodal imaging strategies. We also discuss challenges impeding the clinical translation of NIRF nanoprobes for molecular imaging of cancer. Whereas utilization of most NIRF nanoprobes remains at a proof-of-principle stage, optimizing the impact of nanomedicine in cancer patient diagnosis and management will probably be realized through persistent interdisciplinary amalgamation of diverse research fields.

Section snippets

Molecular imaging and nanotechnology

Cancer molecular imaging is an evolving field in which diverse optical tools and strategies are used for early detection and management of tumors. This field arose from the merger of several pre-existing disciplines, such as modern cancer molecular biology, chemistry and imaging technologies. Consequently, cancer molecular imaging has created unique opportunities to study and noninvasively monitor tumor genesis, development and metastasis in vivo1, 2. It is expected to provide more

Development of NIRF nanoprobes

Although the number of NIRF nanoprobes is rapidly increasing, most of them can be classified into two major categories: downconversion (DCN) and upconversion (UCN) NIRF nanoprobes. DCN nanoprobes produce low energy fluorescence when they are excited by high energy light. The well-established DCN NIRF nanoprobes include NIRF dye-containing nanoparticles, quantum dots (QDs), SWNTs and metal nanoclusters (Figure 1). By contrast, UCN nanoprobes, which are emerging as a new class of fluorescent

NIRF nanoprobes for cancer molecular imaging

One of the major concerns for imaging with NIRF nanoparticles in living subjects is specificity. Three approaches have been applied for tumor targeting of NIRF nanoparticles: (i) the well-known EPR effect; (ii) molecular targeting via specific antigens or overexpressed receptors on the surface of cancer cells; and (iii) the chemical activation of the nanoprobes in specific tumor microenvironments (e.g. enzymatic cleavage or oxidation).

Multimodality imaging

The combination of multiple imaging modalities can yield complementary information and offers synergistic advantages over any single modality. Compared to other imaging agents, nanoparticles have the advantages of multifunctionality and enormous flexibility, allowing for the integration of multimodality reporting moieties, targeting ligands and even therapeutic components into one entity. The development of multifunctional nanomaterials with distinct properties makes it possible to accomplish

Pharmacokinetics and toxicity of NIRF nanoprobes

Comprehensive insights on how NIRF nanoprobes enter, distribute and leave living subjects are vital towards designing NIRF nanoprobes suitable for molecular imaging. To have a critical level of NIRF nanoprobes entering the tumor site, they must avoid uptake by both RES and MPS; however, many systemically injected NIRF nanoprobes can be rapidly cleared from the bloodstream by RES and MPS uptake, leading to accumulation and retention in the liver and spleen. Therefore, the development of NIRF

Challenges and perspectives

Recent and rapid development of synthesis technologies for nanomaterials has created enormous opportunities for the design of specific and sensitive NIRF nanoprobes for cancer molecular imaging. The potential to diagnose and monitor altered physiological changes of cancer in patients by using NIRF nanoprobes is coming closer to reality. However, there remain considerable challenges pertaining to applications of NIRF nanoprobes in humans. In addition to the purity, dispensability and stability

Acknowledgments

This research was partially supported by National Cancer Institute/National Institutes of Health (NCI/NIH) R21 CA121842 (to Z.C.), NCI In vivo Cellular and Molecular Imaging Centers (ICMIC) P50 (to S.S.G.) and NCI Center for Cancer Nanotechnology Excellence Grant U54 CA119367 (to S.S.G.).

Glossary

Fermi wavelength: the size scale is related to E_Fermi/N^1/3, predicted by the free-electron model of metallic behavior (approximately 0.5 nm for gold and silver). E_Fermi (Fermi energy) is the energy of the highest occupied quantum state in a system of fermions at absolute zero temperature.
Fluorescence-mediated tomography (FMT): a method of molecular imaging shows the distribution of a NIRF probes in the region of an animal by three-dimensional tomographic images.
Raman signatures: the Raman spectrum of

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Trends in Molecular Medicine

ReviewNear-infrared fluorescent nanoprobes for cancer molecular imaging: status and challenges

Section snippets

Molecular imaging and nanotechnology

Development of NIRF nanoprobes

NIRF nanoprobes for cancer molecular imaging

Multimodality imaging

Pharmacokinetics and toxicity of NIRF nanoprobes

Challenges and perspectives

Acknowledgments

Glossary

Adv. Drug Deliv. Rev.

Curr. Opin. Chem. Biol.

Adv. Funct. Mater.

Adv. Drug Deliv. Rev.

Curr. Opin. Chem. Biol.

Nat. Biotechnol.

Curr. Opin. Biotechnol.

Nano Today

Biochem. Biophys. Res. Commun.

Adv. Drug Deliv. Rev.

Adv. Drug Deliv. Rev.

Molecular imaging in living subjects: seeing fundamental biological processes in a new light

Genes Dev.

Molecular imaging in cancer

Science

FDG-PET and beyond: molecular breast cancer imaging

J. Clin. Oncol.

Imaging in the era of molecular oncology

Nature

Molecular imaging in drug development

Nat. Rev. Drug Discov.

PET of vascular endothelial growth factor receptor expression

J. Nucl. Med.

Functional brain SPECT – the emergence of a powerful clinical method

J. Nucl. Med.

Multifunctional magnetic nanoparticles: design, synthesis, and biomedical applications

Acc. Chem. Res.

Fluorescence imaging of tumors in vivo

Curr. Med. Chem.

Near-infrared quantum dots as optical probes for tumor imaging

Curr. Top. Med. Chem.

Nanoparticles for molecular imaging – an overview

Endocrinology

Nanoparticles for photoacoustic imaging

Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.

Carbon nanotubes as photoacoustic molecular imaging agents in living mice

Nat. Nanotechnol.

Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging

Nat. Med.

In vivo near-infrared fluorescence imaging of cancer with nanoparticles-based probes

Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol.

Lanthanide-doped fluoride nanoparticles: luminescence, upconversion, and biological applications

Int. J. Nanotechnol.

Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer

ACS Nano

Near-infrared fluorescent labeled peptosome for application to cancer imaging

Bioconjug. Chem.

Synthesis and evaluation of a stable bacteriochlorophyll-analog and its incorporation into high-density lipoprotein nanoparticles for tumor imaging

Bioconjug. Chem.

Nanoparticulate assemblies of amphiphiles and diagnostically active materials for multimodality imaging

Acc. Chem. Res.

Long-circulating near-infrared fluorescence core-cross-linked polymeric micelles: synthesis, characterization, and dual nuclear/optical imaging

Biomacromolecules

Pharmacokinetics and biodistribution of near-infrared fluorescence polymeric nanoparticles

Nanotechnology

Semiconductor nanocrystals as fluorescent biological labels

Science

Quantum dot bioconjugates for ultrasensitive nonisotopic detection

Science

Quantum dots for live cells, in vivo imaging, and diagnostics

Science

Self-assembled nanoscale biosensors based on quantum dot FRET donors

Nat. Mater.

Semiconductor quantum dots for bioanalysis

Angew. Chem. Int. Ed.

Hybrid approach to the synthesis of highly luminescent CdTe/ZnS and CdHgTe/ZnS nanocrystals

J. Am. Chem. Soc.

Engineering InAsxP1-x/InP/ZnSe III-V alloyed core/shell quantum dots for the near-infrared

J. Am. Chem. Soc.

Review
Near-infrared fluorescent nanoprobes for cancer molecular imaging: status and challenges

Engineering InAs_xP_1-x/InP/ZnSe III-V alloyed core/shell quantum dots for the near-infrared