Nanoparticles for improving cancer diagnosis

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Abstract

Despite the progress in developing new therapeutic modalities, cancer remains one of the leading diseases causing human mortality. This is mainly attributed to the inability to diagnose tumors in their early stage. By the time the tumor is confirmed, the cancer may have already metastasized, thereby making therapies challenging or even impossible. It is therefore crucial to develop new or to improve existing diagnostic tools to enable diagnosis of cancer in its early or even pre-syndrome stage. The emergence of nanotechnology has provided such a possibility. Unique physical and physiochemical properties allow nanoparticles to be utilized as tags with excellent sensitivity. When coupled with the appropriate targeting molecules, nanoparticle-based probes can interact with a biological system and sense biological changes on the molecular level with unprecedented accuracy. In the past several years, much progress has been made in applying nanotechnology to clinical imaging and diagnostics, and interdisciplinary efforts have made an impact on clinical cancer management. This article aims to review the progress in this exciting area with emphases on the preparation and engineering techniques that have been developed to assemble “smart” nanoprobes.

Introduction

Cancer accounts for approximately one-fourth of all deaths in the United States [1]. Prognosis of cancer patients depends largely on the time and accuracy of finding the primary and any dormant metastasis sites. Identification of these abnormal sites in an early enough stage can significantly reduce the mortality rate. For example, for breast cancer patients, the 5-year survival rate is 98% if the tumor can be diagnosed in stages 0 and I and drops to 85% for stage II and merely 20% for stage IV tumors [2]. Pancreatic cancer, on the other hand, is usually associated with a high mortality rate; about 75% of pancreatic cancer patients die within 1 year after diagnosis [3]. This high death rate stems from the recessive traits exhibited by pancreatic cancer and a lack of an effective early detection means. Needless to say, there is an urgent need for new tools that can detect cancer in the early or even pre-syndrome stage. Significant progress has been made recently thanks to advances in proteomics and genomics. These burgeoning techniques have identified various biomarkers whose abnormal regulations are closely associated with tumorigenesis and progression [4], [5], [6]. In addition, new screening technologies have been established allowing the identification of antibodies, peptide sequences, and nucleic acid aptamers with high affinity towards a specific biomarker [7], [8].

Nanotechnology, which is a multidisciplinary science involving chemistry, biochemistry, physics, and materials science, has found uses in a wide spectrum of medicine-related applications. These include nanoparticle-based imaging, drug delivery, biosensoring, and hyperthermia, and in the past decade, a number of these nanoparticle-based techniques have been translated into clinical applications [9]. Materials exhibit unique physical and biochemical properties when their dimensions are reduced to between several to hundreds of nanometers. By taking advantage of these unique characteristics, one can develop nanodevices that can sense and monitor biological events with unprecedented efficiency and sensitivity. When coupled to the aforementioned targeting ligands, one can produce “smart” nanoprobes that can interact with a biological system and sense changes on the molecular level. This can take place in vivo, where nanoprobes are systematically administrated, accumulated in tumors through ligand–biomarker interaction, and send out signals for sensitive diagnostic imaging. The nanoprobes are also useful to in vitro diagnosis and analysis of biological samples such as saliva, blood, and urine. Both applications are invaluable and hold great promise in revolutionizing cancer management [9]. The objective of this article is to review the recent progress in this exciting area. We will begin by discussing common tumor biomarkers and their corresponding targeting molecules, followed by a systematic description of the design and fabrication of magnetic nanoparticle-, quantum dot-, upconversion nanoparticle-, and gold nanoparticle-based diagnostic techniques, as well as their potential applications to cancer detection.

Section snippets

Tumor biomarkers

Tumor biomarkers are substances found in blood, urine, stool, or tissues of patients with cancer. They are commonly proteins that are elevated in either cancer cells or other cells in the body in response to cancerous conditions. Measuring biomarker levels is one of the most common methods to detect, diagnose, and manage cancer.

Based on their location, protein biomarkers can be divided into three categories: intracellular, extracellular, and those that are on the cell membrane. In

Engineering of nanoparticles for tumor detection

Nanoparticles can be used as probes in in vivo imaging, biosensing, and immunostaining because nanoparticle-based probes offer many advantages. First of all, they deliver high sensitivity. Many nanoscale materials show unique magnetic, optical, or acoustic properties and they can be further imparted with other types of imaging functionalities to result in probes with multimodal abilities. Secondly, their size is appropriate. Most nanoparticles have a size that is above the threshold of renal

Conclusion and perspectives

This article reviews recent developments in the engineering of nanoparticles used in cancer imaging and diagnosis. With unique physical properties, these nanostructures can revolutionize a number of imaging modalities. For instance, magnetic nanoparticles can serve as contrast probes in MRI, and QDs and UCNPs can function as probes in fluorescence imaging. Depending on the nanostructure, GNPs can find applications in OCT imaging, PA imaging, or CT imaging. Extensive work conducted on small

Acknowledgments

This work was jointly supported by an NCI/NIH R00 grant (5R00CA153772), a UGA startup grant, Hong Kong Research Grants Council (RGC) General Research Funds (GRF) No. CityU 112212 and City University of Hong Kong Applied Research Grant (ARG) No. 9667066. T. Todd was partially supported by a Philbrook scholarship.

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