Quantum Dots in Cancer Cell Imaging

*Salar Khaledian, Mohadese Abdoli, Reza Fatahian and Saleh Salehi Zahabi*

#### **Abstract**

Research on quantum dots (QDs) as zero-dimensional nanostructures whose size is not more than a few nanometers has accelerated in the last two decades, especially in the field of medicine. These nanostructures have attracted much attention due to their unique features such as broad excitation range, narrow emission, strong fluorescence, and high resistance to photobleaching. In this chapter, besides common QDs such as cadmium (Cd)-containing semiconductor QDs, other QDs including carbon-based QDs, chalcogenide QDs, and black phosphorus QDs will be discussed. In addition to describing the optical characteristics of these nanostructures, the usual synthesis methods, their modification and cytotoxicity will be reviewed. Finally, the application of each category of QDs in cancer cell imaging will prospect in more detail.

**Keywords:** cell imaging, semiconductor QDs, carbon-based QDs, MoS2 QDs, black phosphorus QDs

## **1. Introduction**

Cancer is one of the main causes of death all over the world, and after cardiovascular diseases, it is the most common cause of death. This disease is usually caused by defects in the functioning of the regulatory mechanisms of the process of cell growth and division [1]. In the United States alone, 600,000 people die from cancer each year and 1.7 million new cases are diagnosed [2]. Reducing mortality, increasing survival, improving patients, quick diagnosis, and then timely and specific treatments are the keys to success in cancer treatment [3]. Early diagnosis of cancer is important because the length of the treatment period is shortened and treatment costs are reduced. In addition, some cancers are aggressive and asymptomatic in their early stages, and their rapid detection can be very critical [4]. Microscopic imaging techniques (optical and fluorescence), despite having advantages such as inexpensiveness, non-invasive, and ease of use, also have limitations, among which the emission of fluorescence from cancer cell proteins and also the short time of fluorescence emission. The use of small fluorescent dyes (such as 5-aminolevulinic acid, methylene blue, and indocyanine green) can be an entrepreneur in this regard, but cytotoxicity, photobleaching, and rapid clearance through the lymph system limit their use [5]. Clinical methods of cancer imaging include X-ray computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography

(PET), etc., which, despite providing appropriate morphological data of cancer cells and tissue, but in cases where the cancer tissue is very similar to healthy tissue, the resolution and contrast are not appropriate [6, 7]. Therefore, the development of probes that overcome the challenges associated with signal intensity, stability, and tissue penetration will be essential for more extensive clinical implementation. QDs, often described as "artificial atoms," are semiconductor nanocrystals that are in the nanoscale region in all dimensions (so-called zero-dimensional nanostructures) and have a size less than 10 nm [8]. Tunable emission into the NIR region, broad excitation range, narrow emission, and a large Stokes shift, high photoluminescence quantum yield, long photoluminescence lifetime and compatible with biomolecular functionalization and the EPR effect among the attractive optical characteristics of QDs as fluorescent imaging probes [2]. Participation in reactions as catalysts or energy acceptor, or direct oxidation and simultaneous energy transfer are among the mechanisms of QDs to enhance signal intensity [9]. Furthermore, light emission for broad-spectrum excitation of the QDs, emits light at a longer wavelength and enhances tissue penetration [10]. In addition, due to the large surface area of QDs, they can covalently link to biorecognition molecules, such as peptides, antibodies, nucleic acids, or small-molecule ligands for further application as fluorescent probes [11, 12]. Molecular beam epitaxy (MBE), ion implantation, electron-beam lithography, X-ray lithography, wet-chemical, and vapor-phase methods are common methods of quantum dot synthesis, which fall into two general categories: top-down and bottom-up [5]. In the last years, QDs have been extensively studied in biosensing, in vitro diagnosis, cancer treatment, bioimaging, drug delivery, etc. [13–16]. Currently, QDs are widely used for optical imaging of cancer cells, which has great significance for clinical diagnosis. Herein, we briefly introduce typical QDs (semiconductor QDs, carbon-based QDs, chalcogenide QDs and black phosphorus QDs), review the different synthesis methods and modifications, and analyze their cytotoxicity. Finally, the applications of QDs in cancer cell imaging are prospected.
