Cancer diagnostics

Bin Liu

Prof. Bin Liu received her BSc and MSc in Organic Chemistry from Nanjing University and PhD degree in Chemistry from the National University of Singapore (NUS) in 2001. After postdoctoral training and working as an assistant research professor at the University of California, Santa Barbara, she joined NUS in 2005. She is currently Provost's Chair Professor and Head of the Department of Chemical and Biomolecular Engineering. Prof. Liu specializes in bringing organic soluble materials into aqueous media, with a focus on the exploration of their unique applications in biomedical research, environmental monitoring and electronic devices. Prof. Liu serves as an Associate Editor for Polymer Chemistry and is a Fellow of the Royal Society of Chemistry and Singapore Academy of Engineering.

James F. Rusling

Prof. James F. Rusling was awarded a BSc in Chemistry from Drexel University in 1969, and a PhD from Clarkson University in 1979. He is a Professor of Chemistry at the University of Connecticut, a Professor of Surgery and member of Neag Cancer Center at UConn Health, and an adjunct Professor of Chemistry at the National Univ. of Ireland, Galway. His current research includes new cancer diagnostics via the detection of biomarker proteins and miRNA, electrochemical and mass spectrometric arrays for toxicity screening, metabolite-induced gene damage, and fundamental bioelectrochemistry. He has authored over 400 research papers and several books, and is a musician interested in Irish and American folk styles.

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Given the continual and often dramatic improvements in cancer therapy, detection at the earliest possible stage of the disease provides excellent prospects for successful treatment. If cancer is discovered in the advanced stages, however, treatment options become more limited. Drugs or surgical approaches that are effective for early stage cancer are often not appropriate for advanced cancers. Thus, there has been strong research activity for several decades toward more effective early cancer detection methods. There is a pressing need for moving these technologies into practical use in clinics and hospitals. Many of these approaches, involving molecular analyses of patient samples and tumor and cell imaging, have benefited immensely from new materials, especially nanomaterials. For example, protein and genetic biomarkers for cancers in blood are being detected with high sensitivity using approaches involving nanomaterials for biomarker capture, isolation and ultrasensitive detection. New materials are driving a number of imaging technologies at the tumor and cell level into high resolution, high sensitivity performance. This themed issue is devoted to a collection of excellent new advances in these fields.

Over the past decades, an unparalleled explosion in the development of diagnostic nanomaterials has resulted from the discovery of materials with superior chemical, physical and optical properties. Conventional cancer diagnosis techniques, such as computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound, have been widely used in cancer screening and both pre- and post-treatment imaging evaluation. Based on these traditional imaging techniques, the pursuit of improved imaging resolution and reduced biological toxicity has urged the study on nanomaterials to utilize their superior properties for the early detection of cancers. In this themed issue, we bring together original research works from various disciplines to develop a wealth of nanomaterials, both inorganic and organic, for diverse cancer diagnostic applications.

As the most widely used clinical imaging modality, CT plays an important role in cancer diagnosis and treatment. Conventional clinically practice has been using iodine-based small molecules as the CT contrast agents, which are inefficient due to the lack of tumor targeting function and may potentially cause vasodilatation and renal impairment. Over the years, various inorganic nanomaterials, especially gold nanoparticles, have been demonstrated as excellent CT imaging contrast agents, which may overcome the drawbacks of iodine-based agents. In the full paper by Zhang et al. (DOI: 10.1039/c7tb02643a), gold nanorods integrated with InP/ZnS quantum dots have been explored for potential CT and fluorescence dual-modal imaging applications with the advantages of prolonged blood circulation time and high tumor-targeting efficiency. The full paper by Wang et al. (DOI: 10.1039/c7tb02842c) also utilizes the superior optical properties of gold nanorods. Through integration with rare earth doped NaGdF₄, the prepared upconversion nanorods show potential in fluorescence–thermal–MRI multi-modal imaging and photothermal therapy. In addition to CT, MRI is also a widely utilized tool for clinical cancer diagnostics with gadolinium-based and magnetic nanomaterials as the most commonly studied MRI contrast agents. MRI enjoys the advantages of good spatial resolution and unlimited penetration depth while it suffers from drawbacks such as time-consuming operation and cumbersome instrumentations. Thus, developing multimodal contrast agents by integrating MRI with other imaging modality, such as photoacoustic or fluorescence imaging, to obtain complementary information has drawn enormous research attention, as demonstrated by Yang et al. (DOI: 10.1039/c7tb02145c) and Rabyk et al. (DOI: 10.1039/c7tb02888a), respectively.

As a simple and versatile imaging modality, fluorescence imaging has the advantages of superb spatial and temporal resolution. Compared to conventional imaging techniques, it requires less cumbersome instrumentation and image acquisition time, which are ideal for fast and convenient clinical imaging translation. In the full paper by Lee et al. (DOI: 10.1039/c7tb01560g), near infrared fluorescence imaging has been explored for the detection of intracellular glutathione with two newly synthesized cyanine-based probes. In recent years, the enormous research interest in fluorescence imaging has been extended to fluorescent materials with aggregation-induced emission (AIE) characteristics, which overcome the notorious aggregation-caused quenching phenomenon. Through preparing organic nanoparticles with a high loading of AIE luminogens (AIEgens), the obtained super bright AIE nanoparticles have been realized for cellular imaging and two-photon lung vasculature imaging, as reported by Liu et al. (DOI: 10.1039/c8tb00386f). Further advancement of AIEgens involves the development of versatile theranostic materials for both cancer diagnosis and therapy. In a full paper by Ji et al. (DOI: 10.1039/c7tb02685d), a new AIEgen has been synthesized and applied for the selective fluorescence detection and photodynamic ablation of cancer cells, utilizing the concept of enzyme-instructed self-assembly. Moreover, compared with traditional one-photon excited photodynamic therapy (PDT), two-photon PDT is capable of offering a precise and effective treatment at a deeper penetration depth. A full paper by Jiang et al. (DOI: 10.1039/c7tb02609a) reported the development of an AIEgen with mitochondrial targeting ability and efficient generation of reactive oxygen species while susceptible to two-photon excitation. Building upon fluorescence imaging, a series of excellent works have focused on the delicate design of nanomaterials to address critical medical problems in cancer diagnostics. Chen et al. (DOI: 10.1039/c7tb01989k) have designed a novel prodrug nano-system, where fluorescence is activated by internal enzyme stimuli for cancer detection and also utilized as a photon-trigger for the release of an anticancer drug. It has been demonstrated as a proof-of-concept for cancer detection and on-demand selective ablation of cancer cells upon both internal and external activation. Another interesting work by Yan et al. (DOI: 10.1039/c8tb00076j) reports the development of a multifunctional nano-formulation based on polydopamine nanoparticles which can realize cell ablation through synergistic effect from a cell cycle inhibitor and a photosensitizer.

In the course of tumorigenesis, various cancer biomarkers, such as proteins, peptides and miRNA, would be released by cancer cells in response to different phases of cancer progression. It is of utmost importance to identify and detect the biomarkers for the early detection of cancers. Kim et al. (DOI: 10.1039/c7tb02180a) have proposed the strategy of designing redox-responsive folate fluorophore conjugates to specifically target the folate receptor-positive cancer cells with near infrared fluorescence imaging. With a similar conceptual design, a mitochondrial-specific fluorescence probe targeting a biomarker has been developed by Gao et al. (DOI: 10.1039/c7tb03200e) and validated in acute ischemia models. Moreover, in the communication by Lin et al. (DOI: 10.1039/c8tb00404h), a highly sensitive biosensor composed of ruthenium carbonyl clusters on monolayer graphene has been developed for the detection of matrix metalloproteinase-2 (MMP-2), which is a biomarker for stroke and cancer-related diseases. The review by Zhao et al. (DOI: 10.1039/c7tb02541f) provides some deeper insights and a broader understanding of how these biomarkers in vivo can be targeted by polypeptide-based nanomaterials, which exhibit advantages such as low immunogenicity and good biodegradability. Specifically, this review focuses on the applications of detection, imaging and treatment of breast cancer with functional polypeptide nanomaterials.

Being the guest editors of this themed issue on cancer diagnostics, we hope that this themed issue is able to bring intellectual stimulation to a broad group of researchers and clinicians. The distinctive original research content should serve not only as a valuable knowledge pool for researchers, but also as a source of inspiration for innovative ideas about advancing cancer diagnosis with diverse imaging techniques, followed by different treatment strategies.

We wish to express our gratitude to all the contributors for all the fascinating work that has shaped this themed issue. We would also like to thank the Royal Society of Chemistry and Journal of Materials Chemistry B for the firm support in creating this themed issue on cancer diagnostics.

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