Elsevier

The Lancet Oncology

Volume 7, Issue 8, August 2006, Pages 657-667
The Lancet Oncology

Review
Emerging use of nanoparticles in diagnosis and treatment of breast cancer

https://doi.org/10.1016/S1470-2045(06)70793-8Get rights and content

Summary

The biological application of nanoparticles is a rapidly developing area of nanotechnology that raises new possibilities in the diagnosis and treatment of human cancers. In cancer diagnostics, fluorescent nanoparticles can be used for multiplex simultaneous profiling of tumour biomarkers and for detection of multiple genes and matrix RNA with fluorescent in-situ hybridisation. In breast cancer, three crucial biomarkers can be detected and accurately quantified in single tumour sections by use of nanoparticles conjugated to antibodies. In the near future, the use of conjugated nanoparticles will allow at least ten cancer-related proteins to be detected on tiny tumour sections, providing a new method of analysing the proteome of an individual tumour. Supermagnetic nanoparticles have exciting possibilities as contrast agents for cancer detection in vivo, and for monitoring the response to treatment. Several chemotherapy agents are available as nanoparticle formulations, and have at least equivalent efficacy and fewer toxic effects compared with conventional formulations. Ultimately, the use of nanoparticles will allow simultaneous tumour targeting and drug delivery in a unique manner. In this review, we give an overview of the use of clinically applicable nanoparticles in oncology, with particular focus on the diagnosis and treatment of breast cancer.

Introduction

Nanobiotechnology, defined as biomedical applications of nano-sized systems, is a rapidly developing area within nanotechnology. Nanomaterials, which measure 1–1000 nm, allow unique interaction with biological systems at the molecular level. They can also facilitate important advances in detection, diagnosis, and treatment of human cancers and have led to a new discipline of nano-oncology.1, 2 Nanoparticles are being actively developed for tumour imaging in vivo, biomolecular profiling of cancer biomarkers, and targeted drug delivery. These nanotechnology-based techniques can be applied widely in the management of different malignant diseases.

Some breast cancers express protein biomarkers (eg, oestrogen receptor, progesterone receptor, and ERBB2) on which therapeutic decisions are made. Semiconductor fluorescent nanocrystals, such as quantum dots, have been conjugated to antibodies, allowing for simultaneous labelling and accurate quantification of these target proteins in one breast tumour section (figure 1).3 The use of nanoparticles—not only quantum dots of different sizes and emission spectra, but also gold-containing nanoparticles (ie, Raman probes)—will allow the simultaneous detection and quantification of several proteins on small tumour samples, which will ultimately allow the tailoring of specific anticancer treatment to an individual patient's specific tumour protein profile.4 The ability to detect molecular targets simultaneously on individual tumour samples could allow correlation between gene products and proteins in real time.5 In addition, the effects of an individual treatment on expression of the target protein can be monitored before and after treatment, and provide a rapid method to measure the efficacy of a targeted therapy.

Nanotechnological approaches (eg, nanocantilevers and nanoprobes) are being actively investigated in cancer imaging.6 Nanoparticles coupled with cancer-specific targeting ligands can be used to image tumours and detect peripheral metastases.7 Supermagnetic nanoparticles that have a metal core and are bioconjugated with antibodies against ERBB2 have shown promising results for simultaneous imaging and targeting of breast cancers therapeutically in vivo.8 Moreover, nanoparticles conjugated to cancer-specific ligands could be used in early identification of tumours, allowing early intervention with a chemopreventive agent.

Several nanotechnological approaches have been used to improve delivery of chemotherapeutic agents to cancer cells with the goal of minimising toxic effects on healthy tissues while maintaining antitumour efficacy. Doxorubicin has been formulated with a liposome delivery system into nanoparticle size (figure 2), which maintains the efficacy of the drug and decreases cardiac toxic effects.9, 10 One of these delivery systems, pegylated liposomal doxorubicin, is approved for treatment of refractory ovarian cancer and Kaposi's sarcoma in the USA. Nanoparticle albumin-bound (NAB) paclitaxel also has greater efficacy than conventional castor-oil-based paclitaxel with an improved safety profile,11, 12 and is approved in the USA for treatment of metastatic breast cancer.

The use of nanotechnology in cancer encompasses many nanotechnological approaches, and it would be impossible to cover these in a single review. We have therefore focused this review on the emerging use of nanoparticles in breast cancer.

Section snippets

Types of biomedical nanoparticles

Although the number of different types of nanoparticles is increasing rapidly, most can be classified into two major types: particles that contain organic molecules as a major building material (figure 1) and those that use inorganic elements, usually metals, as a core (figure 2). Liposomes, dendrimers, carbon nanotubes, emulsions, and other polymers are a large and well-established group of organic particles. Use of these organic nanoparticles has already produced exciting results.13, 14, 15,

Profiling of biomarkers

With the increasing use of targeted therapies in oncology, it is imperative that methods of molecular profiling are optimised. The success of many targeted treatments depends on the expression of specific proteins or genes present in cancer cells. For example, in breast cancers, the level of hormone-receptor expression correlates directly with the benefit of endocrine treatments, and the presence of HER2 protein overexpression or gene amplification, or both, is a prerequisite for benefit from

Treatment of breast cancer

Tumour-selective delivery of anticancer agents is desirable to increase the cell-kill effect, while protecting the healthy tissue from exposure to a cytotoxic agent, thereby reducing systemic toxic effects, and nanoparticles could be used for this purpose. Much preclinical research has been done on the use of nanoparticles as a means of targeted therapy in oncology. Some of these ideas have already been brought into the clinic. We will focus on the use of nanoparticle formulations in the

Conclusion

The use of nanotechnology in oncology offers exciting possibilities, and is regarded an area of major importance by the US National Cancer Institute, which has recently awarded several Center of Cancer Nanotechnology Excellence grants. The use of nanoparticles conjugated to antibodies allows the possibility of simultaneously detecting multiple molecular targets in small tumour samples, on which treatment decisions can be made. Protein and gene expression in an individual tumour can be

Search strategy and selection criteria

References were obtained by searches of PubMed using the MeSH search terms “nanotechnology”, “nanoparticles”, “breast cancer”, “diagnostics”, “quantum dots”, “Raman probes”, “dendrimers”, “magnetic nanoparticles”, “liposomes”, “carbon nanotubes”, “abraxane”, “treatment”, with additional search terms “biomarkers”, “profiling”, “in-vivo imaging”, “targeting”, and “small interfering RNA” required for specific aspects of the review. Only papers published between January, 1980, and December,

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