Cancer nanotechnology: opportunities and challenges

Key Points

  • Nanotechnology concerns the study of devices that are themselves or have essential components in the 1–1,000 nm dimensional range (that is, from a few atoms to subcellular size).

  • Two main subfields of nanotechnology are nanovectors — for the administration of targeted therapeutic and imaging moieties — and the precise patterning of surfaces.

  • Nanotechnology is no stranger to oncology: liposomes are early examples of cancer nanotherapeutics, and nanoscale-targeted magnetic resonance imaging contrast agents illustrate the application of nanotechnology to diagnostics.

  • Photolithography is a light-directed surface-patterning method, which is the technological foundation of microarrays and the surface-enhanced laser desorption/ionization time-of-flight approach to proteomics. Nanoscale resolution is now possible with photolithography, and will give rise to instruments that can pack a much greater density of information than current biochips.

  • The ability of nanotechnology to yield advances in early detection, diagnostics, prognostics and the selection of therapeutic strategies is predicated based on its ability to 'multiplex' — that is, to detect a broad multiplicity of molecular signals and biomarkers in real time. Prime examples of multiplexing detection nanotechnologies are arrays of nanocantilevers, nanowires and nanotubes.

  • Multifunctionality is the fundamental advantage of nanovectors for the cancer-specific delivery of therapeutic and imaging agents. Primary functionalities include the avoidance of biobarriers and biomarker-based targeting, and the reporting of therapeutic efficacy.

  • Thousands of nanovectors are currently under study. By systematically combining them with preferred therapeutic and biological targeting moieties it might be possible to obtain a very large number of novel, personalized therapeutic agents.

  • Novel mathematical models are needed, in order to secure the full import of nanotechnology into oncology.

Abstract

Nanotechnology is a multidisciplinary field, which covers a vast and diverse array of devices derived from engineering, biology, physics and chemistry. These devices include nanovectors for the targeted delivery of anticancer drugs and imaging contrast agents. Nanowires and nanocantilever arrays are among the leading approaches under development for the early detection of precancerous and malignant lesions from biological fluids. These and other nanodevices can provide essential breakthroughs in the fight against cancer.

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Figure 1: Multifunctional nanoparticle.
Figure 2: Nanotechnologies for molecular detection, identification and diagnostics.
Figure 3: Nanowires and nanocantilevers.
Figure 4: Multicomponent targeting strategies.
Figure 5: A vision for a future multistage nanodevice with multiple-barrier-avoidance capability.

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Acknowledgements

The author is indebted to A. Barker, R. Duncan, L. Hartwell, L. Liotta, R. Smalley, A. von Eschenbach and S. Venuta for discussions and recommendations. The assistance in the literature review by J. Alper, M. Chang, M. Merlo, J. Sakamoto and P. Sinha is gratefully acknowledged. Support for this work was provided by The Ohio State University College of Medicine and Public Health, the National Cancer Institute's Office of Technology and Industrial Relations, and the State of Ohio's Biomedical Research and Technology Transfer programme.

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Through his patents, the author has a financial interest in research presented in references 27, 38–39, 51, 66–68, 70, 71, 81, 114 and 123. iMEDD Inc. of Foster City, California, posseses commercial rights on several of the author's patents. The author is a shareholder, consultant and Chair of the Scientific Advisory Board of iMEDD Inc. He is Editor in Chief of the archival journal Biomedical Microdevices: BioMEMS and Biomedical Nanotechnology.

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DATABASES

Entrez Gene

annexin-V

BRCA1

CEA

EGF

PSA

National Cancer Institute

breast cancer

Kaposi's sarcoma

melanoma

ovarian cancer

prostate cancer

FURTHER INFORMATION

Abraxane

National Cancer Institute Alliance for Nanotechnology in Cancer

National Nanotechnology Initiative

Glossary

NANOVECTOR

A hollow or solid structure, with diameter in the 1–1,000 nanometre range, which can be filled with anticancer drugs and detection agents. Targeting moieties can also be attached to the surface. Nanovectors can be used for targeted gene therapy.

LIPOSOME

A type of nanovector made of lipids surrounding a water core.

NANOPARTICLE

A solid nanovector, typically made of a single material.

RETICULO-ENDOTHELIAL SYSTEM

A system composed of monocytes and macrophages that is located in reticular connective tissue (for example, in the spleen). These cells are responsible for phagocytosing and removing cellular debris, pathogens and foreign substances from the bloodstream.

NANOSHELLS

A nanoparticle composed of a gold shell surrounding a semiconductor. When nanoshells reach their target they can be irradiated to make the nanoshell hot — the heat kills the cancer cell.

NANOCANTILEVERS

Flexible beams, resembling a row of diving boards, that can be coated with molecules capable of binding to cancer biomarkers.

NANOWIRES

Nanoscale sensing wires that can be coated with molecules such as antibodies to bind to proteins of interest and transmit their information through electrodes to computers.

FULLERENE

A nanoscale structure, composed of carbon atoms arranged in a specific soccer-ball-like architecture. Fullerenes are a form of carbon (C-60), which also forms nanotubes.

NANOTUBES

Cylinder-like assemblies of carbon atoms, with cross-sectional dimensions in the nanometre range, and lengths that can extend over a thousand times their diameters.

CELL XENOGRAFTS

Cross-species, therapeutic cell transplants.

SENTINEL LYMPH-NODE BIOPSY

A surgical approach for the assessment of the metastatic involvement of lymph nodes. It is based on the hypothesis that if the node that is nearest to a tumour is negative, the others along the same pattern of spread will also be negative.

QUANTUM DOTS

Semiconductor particles with an inert polymer coating. The material used for the core can be chosen depending on the emission wavelength range being targeted. Targeting molecules can be attached to the coating.

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Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nat Rev Cancer 5, 161–171 (2005). https://doi.org/10.1038/nrc1566

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