What’s quantum dot for cancer?

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Abstract​

Cancer is a major threat to public health in the 21st century because it is one of the leading causes of death worldwide. The mechanisms of carcinogenesis, cancer invasion, and metastasis remain unclear. Thus, the development of a novel approach for cancer detection is urgent, and real-time monitoring is crucial in revealing its underlying biological mechanisms. With the optical and chemical advantages of quantum dots (QDs), QD-based nanotechnology is helpful in constructing a biomedical imaging platform for cancer behavior study. This review mainly focuses on the application of QD-based nanotechnology in cancer cell imaging and tumor microenvironment studies both in vivo and in vitro, as well as the remaining issues and future perspectives.

KEY WORDS: quantum dots, molecular imaging, multimodality probes

 

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Introduction​

Cancer remains a global public health problem as the leading cause of death in developed countries and the second leading cause of death in developing countries[1]. It is a diverse group of diseases affecting a variety of tissues, but is generally characterized by the uncontrolled proliferation of abnormal cells, with the ability to invade surrounding tissues, and possibly metastasize. Over the past few decades, numerous studies have focused on the regulation of cell adhesion and cytoskeletal dynamics as the mechanisms of cancer invasion and progression[2-4]. However, they have largely failed to define the rate-limiting mechanisms that govern cancer invasion and progression, such as the dominant signaling pathway, receptor–ligand interactions, or protease–substrate interactions. At present, cancer invasion is regarded as a heterogeneous and adaptive process with a tumor microenvironment [5]. The tumor microenvironment, composed of tumor stromal components, host cells, and adjacent supporting tissues, is an intrinsic element because of its dynamic interactions with the tumor for continued tumor growth and progression[6,7]. Once the tumor microenvironment responds to the tumor cells, components such as fibroblasts, endothelial cells, and macrophages could be activated and could release functional factors that promote or inhibit cancer invasion[8-14]. Thus, tumor cells influence the microenvironment and vice versa, jointly driving cancer progression in a reciprocal manner[15,16]. Thus, to intensively explain the mechanism of cancer invasion and progression, understanding the biological behavior during tumor progression is necessary, and the appropriate approach for understanding the biological behavior of cancer should be established.

Nanotechnology is a promising platform in cancer molecular imaging. Quantum dots (QDs) are being intensively studied as a novel probe for biomedical imaging both in vitro and in vivo because of their unique optical and electronic characteristics. To overcome the obstacles of QDs for biomedical imaging, the physicochemical properties of QDs such as size, shape, composition, and surface features have been extensively investigated[17-23]. When conjugated with bimolecular agents such as antibodies, peptides or other small molecules, QD-based probes can be used to target cancer molecules with high specificity and sensitivity. Thus, QD-based multiplexed molecular imaging can reveal the tempo-spatial relationship among molecules by simultaneously staining several tumor biomarkers. Several studies have shown that this method is essential for deciphering the molecular mechanism of cancer invasion and is useful for the study of tumor microenvironment[20-22]. In addition to the promising application for molecular imaging in vitro, QD-based multifunctional probes lead to the development of anti-cancer drug and siRNA delivery[24], magnetic resonance imaging (MRI)[25,26], multiplexed molecular cancer diagnosis, and in vivoimaging[27-30]. In this view, QDs can be used to monitor the dynamic changes of a tumor microenvironment, which would greatly contribute in the research of cancer invasion mechanism and guide better clinical personalized therapy. Therefore, compared with conventional imaging approaches, a molecular QD-based targeted nanoplatform offers various advantages. First, hundreds, thousands or even more imaging labels or combinations of labels for different imaging modalities can be attached to a single nanoparticle, which can lead to dramatic signal amplification. Second, multiple, potentially different, targeting ligands on the nanoparticle can provide enhanced binding affinity and specificity. Third, the ability to integrate a specific biomarker to bypass biological barriers can enable enhanced targeting efficacy. Ultimately, the combination of different targeting ligands, imaging labels, therapeutic drugs, and many other agents may allow the effective and controlled delivery of therapeutic agents in patients, which can be noninvasively monitored in real time.

In this review, we summarize the major advances in the application of QD-based nanotechnology for cancer research, including the detection of primary tumor in vitro, tumor imaging in vivo, study of tumor microenvironment for invasion, and progression and multimodality biomedical molecular targeting imaging, as well as the major remaining issues and future perspectives.

 

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