**1. Introduction**

Nowadays, nanomaterials have been applied in most major scientific and industrial fields [1–5]. Such wide ranges of applications are possible owing to the opportuneness of the extremely different classes of nanomaterials with various novel properties. Noticeably, the biocompatibility of the nanomaterials is a great issue for the scientists to use them in the biomedical applications including, among others, biosensors and drug delivery systems.

A biosensor is a device that can produce a measurable signal proportional to the concentration of the biological analyte target [6, 7]. Biosensors are one of the most widely studied topics due to their contributions to development of innovative medicines, which could be applied as adapted drugs or highly sensitive detectors of disease markers [8–15].

Biosensors become new inventions that are hopeful to help an effective diagnosis in the current COVID-19 pandemic and also to remove experimental drugs during the human trials when they show any unwanted adverse effect [16–18]. Generally, a given biosensor has three components including a biological element, a transducer, and a detector [19]. The biological element leads to a detection of the analyte and a generation of a response. This response is thereafter transformed into a detectable signal through a transducer, which is often the most challenging part. Consequently, the generated signal is intensified and processed via an amplifier for exhibiting it by an electronic display device. **Figure 1** schematically illustrates the various steps of the signal processing in a biosensor.

Nanomedicine emerges as a revolutionary medical technology, particularly in the cancer therapy. Recently, much effort has been devoted to the study of nanostructures for applications in nanomedicine domain owing to their particular role in cancer therapies [20–26]. Undoubtedly, the most challenging task in cancer therapy is the finding of a suitable drug delivery system. As the design of efficient and promising drug delivery systems could be developed on the basis of nanostructures, a survey of the relevant prospective drug delivery agents constitutes a primordial subject [27–29].

A key requirement for a drug delivery system is that the delivery of the drug to the targeted sites needs to be associated with a considerable decrease in adverse effects. It is worth mentioning that the experimental research in this field is rather long and expensive, and thereby computational studies can effectively help experimentalists in the design of nanocarriers [30–45]. In this regard, the nature of the interactions between drugs and nanostructures emerges as an essential step. **Figure 2** represents a schematic boron-based drug delivery system.

Boron is an effective element in a wide range of fields. The history of boron chemistry started from the isolation of a series of simple boranes by Stock and his co-workers [46]. In the last two decades, several types of low-dimensional boron nanomaterials such as nanoclusters, nanowires, nanotubes, nanobelts, nanoribbons, nanosheets, and monolayer crystalline sheets have been experimentally synthesized and characterized [47–57]. These boron-based nanomaterials exhibit different bonding patterns from those of bulk boron crystals that exist as the α-, β-, γ-rhombohedral, and α-tetragonal forms. Accordingly, their resulting unique physical and chemical properties are fascinating from a standpoint of materials science. Noticeably, boron-based nanomaterials, such as clusters, can be used as superatoms or building blocks of other nanostructures with novel functionalities and properties.

Of the various types of boron-based nanomaterials, the pure boron clusters (BC) represent a distinctive category of structures owing to their unconventional structures and bonding patterns. During the past decades, boron-based compounds at the

**Figure 1.** *Steps of signal processing in a biosensor.*

*Boron Clusters in Biomedical Applications: A Theoretical Viewpoint DOI: http://dx.doi.org/10.5772/intechopen.106215*

**Figure 2.** *A schematic boron-based drug delivery system.*

nanoscale have been the subject of a large number of theoretical and experimental studies. These systems have intriguing features with different structures such as planar, quasi-planar, ribbon, bowl, cage, teetotum, tubular drum-like forms, multiple ring tubes, and fullerenes [58–72]. This arises from the fact that the boron atom with electron deficiency can take part in both localized and delocalized electronic systems in many geometric shapes. In other words, the most attractive nature of boron skeletons is due to the electron deficiency of the boron atom, leading to a rich bonding capacity.

The neutral Bn clusters with the size of smaller than 20 atoms prefer a planar or quasi-planar structure, except for B14 which has a fullerene-type [73]. The B40, B32C4, and B32Si4 fullerene-like clusters together with the B30 and B36 bowls have attracted some interest in biomedical applications. The schematic structures of B40, B32C4, B32Si4, and B36 are provided in **Figure 3**.

Tai et al. [74] reported a computational study on the structural, electronic properties, and chemical bonding of the bowl-like B30 global-minimum cluster, exhibiting a disk-aromaticity [11]. Similarly, the B36 was theoretically predicted to have a bowl shape stabilized by a disk aromaticity [75]. Piazza et al. [76] subsequently reported an experimental identification of the neutral B36 from the photoelectron spectrum of the B36− anion, confirming a highly stable quasi-planar boron cluster with a central hexagonal hole, providing the first experimental evidence that single-atom layer boron sheets with hexagonal vacancies are potentially viable. The neutral B36 is in fact the smallest boron cluster exhibiting a sixfold symmetry and a hexagonal hole, and it can be viewed as a potential basis for extended two-dimensional boron sheets. Recently, it was revealed that the B364− cluster has a six-membered hole, but the presence of four extra electrons renders the considered system difficult to be synthesized [77]. Thus, the use of carbon or silicon atoms instead of boron anion to neutralize the extra electrons in the carbon or silicon-doped cluster (C4B32 and Si4B32) has been suggested and comprehensively studied [78].

#### **Figure 3.**

*Shapes of the B40, B32C4, B32Si4 fullerenes, and B36 bowl clusters.*

The fullerene B40 was also predicted by computations [75] and subsequently prepared [79] by utilizing a laser vaporization supersonic source and identified via photoelectron spectroscopy (PES). The B40 fullerene with a *D*2d symmetry consists of four heptagonal rings and two hexagonal rings. With exceptional properties, it has been subjected to many theoretical studies due to its potential applications in molecular devices [80–85]. It is noteworthy that its electronic and reactivity features could be tuned via metal encapsulation or substitution.

### *Boron Clusters in Biomedical Applications: A Theoretical Viewpoint DOI: http://dx.doi.org/10.5772/intechopen.106215*

Boron neutron capture therapy (BNCT) for cancer treatment remains the main biomedical application of boron-based compounds [86, 87]. Boron compounds have thus facilitated the mission of BNCT. Furthermore, novel biological activities of boron cages and their complexes have been reported [88, 89].

The drugs that are commonly explored for anticancer treatment include 5-fluorouracil (FU), metronidazole (ML), hydroxyurea (HU), nitrosourea (NU), 6-thioguanine (TG), melphalan (MP), and cisplatin and nedaplatin (cf. **Figure 4**). Some nitrosoureas have been used in chemotherapy for treatment of brain tumors, breast carcinoma, lymphomas, and leukemia. The MP drug is conventionally applied for the treatment of specific cancers such as multiple myeloma, ovarian cancer, and breast cancer. FU also has multiple applications and is one of the most beneficial drugs to date to treat breast, head, neck, anal, stomach, colon, and skin cancers [24]. Cisplatin, which is one of the most common anticancer chemotherapy drugs, is particularly effective in treatment of testis, ovary, esophageal, bladder, non-small-cell lung cancers, and head and neck malignancies [90, 91]. Nedaplatin is also an antineoplastic drug which is used for cancer chemotherapy with the

**Figure 4.** *Structures of the biomolecules and drugs commonly considered.*

purpose to decrease the inherent toxicities induced by cisplatin [92]. However, the long-term use of such drugs may lead to some secondary tumors such as leukemia [93]. Hence, improvement of the efficacy and reduction of the toxicity of these drugs is of great importance. Of the diverse strategies recently put forward, the drug delivery is one of the most widely used techniques to improve the therapeutic efficiency and targeting of various drugs. In this context, the design of boronbased drug delivery systems appears to be an important issue for the beneficial usage of boron clusters.

The main contribution of this chapter is to scrutinize the functionality of calculated predictions for boron clusters to be considered as prospective biosensors or drug delivery systems. The theoretical methodologies will first be presented. A brief discussion on the various features of promising biosensors or drug delivery systems that should further be investigated for biomedical applications.
