**5. Drug delivery application**

 Targeted drug delivery using QDs has appeared to have potential applications in recent times. Since the enhanced efficacy of existing drugs and new developments in therapeutics are made possible by adopting various functionalized QDs for this purpose. Several preliminary and drug trials have demonstrated the potential application of this QD based on theranostic systems at the same time also to achieve reduced drug harmfulness, better quality in bio-compatibility [ 40 ] and bio-availability [ 41 ], enhanced circulation times [ 42 ], precise drug release [ 43 ]

#### *Application of Quantum Dots in Bio-Sensing, Bio-Imaging, Drug Delivery, Anti-Bacterial… DOI: http://dx.doi.org/10.5772/intechopen.107018*

and targeting [44]. Nevertheless, translation of QDs vehicles from bench side to bedside requires a detailed understanding of the impact of these QDs in organic systems when their utility towards in vivo conditions. Recent development in the properties of QDs includes optimized brightness, diminished hydrodynamic dimensions, chemically inert to the environment, and functional groups attached to ligands that are site-specific. Recent studies have shown that Si QDs and fluorescent nanodiamonds are biocompatible, which positions them as excellent diagnostic imaging candidates. Song et al. [45]. Several preliminary and drug-trials have demonstrated the potential application of this QD based on theranostic systems at the same time also to achieve reduced drug harmfulness, better quality in bio-compatibility [40] and bio-availability [41], enhanced circulation times [42], precise drug release [43] and targeting [44]. Nevertheless, translation of QDs vehicles from bench side to bed side requires an in-depth understanding of the impact of these QDs in biological systems when their utility towards in vivo conditions [46]. Recent development in the properties of QDs includes optimized brightness, diminished hydrodynamic dimensions, chemically inert to the environment, and functional groups attached to ligands that are site-specific [47]. Recent studies have shown that Si QDs and fluorescent nanodiamonds are biocompatible, which positions them as excellent diagnostic imaging candidates. Song et al. [48] developed nanoparticles with dual modes of contrast-enhanced CT (CECT) and fluorescence imaging, made of a combination of silica coated-gold nanoformulation/quantum dots (Au-SiO2-QDs). Several research groups are developing nanoparticle-based agents that can diagnose and treat a person through one product.

Quantum dots (QDs) can go about as the primary nanocarrier or be important for additional perplexing structures. Paclitaxel (PTX), cancer-battling drug, is frequently bundled with nanostructured lipid transporters intended to have a theranostic way to deal with malignant growth treatment [49]. It was found to have exemplification adequacy of ~80%. PTX could be supported and delivered in 12 h in mixture of silica

#### **Figure 3.**

*Quantitative multiplex imaging capability in live animals using QD. (A) 1 × 106 ES cells labeled with QD 525, 565, 605, 655 and 705 were subcutaneously injected on the back of nude mice right after labeling and the image was taken with a single excitation light source right after injection. The quantification of fluorescent signal intensity defined as total signal-background/exposure time in millisecond was shown in (B). (image reused under unrestricted reuse permission) [34].*

nanocapsules that were stacked with ZnSe:Mn/ZnS. This core-shell nanoformulation with the anticancer medication PTX. Another study by Cai et al. used Doxorubicin (DOX) on pH-responsive Zinc Oxide quantum dots [50, 51]. In another study, very small QDs were synthesized by the group with a size of approximately 3 nanometer attached with a functional group of poly-ethylene-glycol (PEG) and hyaluronic acid to target glycoprotein CD44 that are overexpressed in malignant growth cells with DOX as the drug model [51]. Under acidic intracellular environment, this medication (DOX) will be delivered. In another study, Yang et al. worked on quercetin (QE) attached with cadmium selenide-zinc sulphide QDs as anticancer and antibacterial nanoformulation and exhibited that QE-attached CdSe-ZnS were more attractive contrary to drug-nontoxic *Escherichia coli* and *Bacillus subtilis* and subsequently quercetin attached cadmium selenide nanoformulation without ZnS [52]. The anti-cancer activity measure was centered around the multiplication and relocation of human gastric epithelial cell lines (BGC-823), which displayed an expansion in cellular toxicity of two-to six-times contrasted with crude Quercetin-CdSe QDs (**Figure 3**) [53].

#### **6. Anti-bacterial activity**

Antibiotics are the main drugs that are used for fighting bacterial contamination and have a significant responsibility in the maintenance of society's wellbeing. Bacterial infections have risen to a public health crisis, with widespread resistance to antibiotics. Graphene or Carbon quantum dots may be used as a new form of antibiotic and could even be applied to biomedical research [54–56]. An increasing threat to the public from bacteria has raised concerns about the spread of drug resistance. A method to limit this development and fight bacterial infections has been found in the use of quantum dots [57]. Widespread bacterial infections—particularly of the hospital-acquired kind—and the spread of antibiotic-resistance plague the medical world. Carbon quantum dots, also known as CQDs, have been investigated for a variety of uses—including as an antibacterial agent.

Bacterial diseases and the spread of antibiotic obstruction address a developing danger to general wellbeing, and the blend of CQDs with antibodies could be a promising sort of antibacterial treatment. The spread of antibacterial-safe microbes is a developing danger to general wellbeing. Carbon quantum dots have turned into a promising antibacterial option since they are non-poisonous to people, they have no known obstruction mechanism. All Gram-positive, and Gram-negative bacteria were found to be inhibited by Carbon QDs [58–62]. Examination of the antibacterial component of positively charged carbon QDs (PC-CQDs) demonstrated that little estimated PC-CQDs functionalized with −NH2 and −NH prompted solid adherence manner on bacterial cell layers [63–65].

Additionally, the passage of PC-CQDs caused conformational changes in the gene and generation of receptive oxygen species in microscopic organisms. Safety assessment represented that PC-CQDs did not set off noticeable drug confrontation or hemolysis. Moreover, PC-CQDs really advanced injury recuperating in rats tainted with blended *Staphylococcus aureus* and *Escherichia coli* by repressing bacterial development while advancing the arrival of inflammatory cytokines and development factors fundamental for tissue repair. A few examinations have revealed the expected antibacterial action of these QDs for genuine injury mending applications in complex bacterial contaminations and, surprisingly, safe microorganisms caused diseases

*Application of Quantum Dots in Bio-Sensing, Bio-Imaging, Drug Delivery, Anti-Bacterial… DOI: http://dx.doi.org/10.5772/intechopen.107018*

[63, 66–69]. Recent research showed the successful application of Quaternized carbon quantum dots (CQDs) which have excellent broad-spectrum antibacterial activity. These Q-CQDs contain electron-withdrawing hydroxyl group (−OH), and electron donating methyl (−OCH3), in addition to tri-methylamin (−N+(CH3)3) groups. Q-CQDs functionalized with −N+(CH3)3 displayed a strong attachment to the membrane of the bacterial cell. Hence it damages the bacterial cell by crossing the membrane and entering the cell. The production of reactive oxygen species (ROS) due to the permeation of Q-CQDs into these bacteria resulted and the efflux of the RNA and DNA in the cytoplasm, which ultimately kills the bacteria. Q-CQDs were also shown to have anti-bacterial activity in treating *S. aureus*, *E. coli*, and mixed *S. aureus*-co-*E. coli* diseased injuries by killing bacteria and stimulating septic wound therapeutic. Further functional groups can be attached to the surface of these QDs and chemical modifications can be done by effective surface engineering strategy to widen their utility to meet specific targeting and guiding needs in numerous disease treatments [70].

#### **7. Photo thermal therapy**

Recent years have seen a lot of interest in photo-thermal therapy (PTT), a negligibly invasive and possibly effective procedure [71, 72]. It is based on the generation of heat for the thermal melting of malignant tumors by activating photosensitizing chemicals by pulsed laser irradiation at near-infrared wavelengths. The main advantages of photothermal therapy over traditional radiotherapy or chemotherapy include the capacity to penetrate deep tissue layers and the little impact of unselected cell death on the healthy adjacent tissue. Large optical frequency absorption cross-sections, low toxicity, simplicity in functionalization, biocompatibility, and is highly soluble in organic solutions are all desirable characteristics of a photosensitizer. Recent years have seen the usage of QDs by researchers to accomplish PTT in malignant cells [73]. In vitro research on the PTT application of CQDs for malignancy treatment was reported by Zhang et al. [74]. When exposed to NIR light, PEGylated (stealth) Carbon-QDs were found to have an abundant capability for photo-thermal treatment with no harmful toxicity beside breast cancer cell lines (MCF-7). Advanced studies have succeeded by the combination of photo-thermal and chemotherapy by linking these CQDs silicon dioxide (SiO2) nanoformulation loaded with doxorubicin (DOX) in the treatment of cancer cells [75]. This study's in vivo tests showed that tumor growth in mouse models might be efficiently controlled without causing cancer to return. Doxorubicin (DOX) administration using nanoplatforms in conjunction with PTT and chemotherapy has been investigated in a number of studies in cancer cell lines.

In addition to DOX, thermo-acoustic nanoplatforms (CdTs) were created that targeted cancer cells that contained lysosomes while also rapidly raising temperature in response to laser irradiation [76]. For targeted gene therapy to malignant cells for suppressing cancer both in vitro and in vivo, therapeutic genes were directly attached to CdTs via electrostatic interactions. Additionally, it was able to simultaneously use CdTs for photo-thermal ablation of cancer cells and photo-acoustic imaging based on the recognition of ultrasonic pulses [77, 78]. In order to create an effective system for image-guided positron treatment, it is crucial to strike a balance between radiative degeneration (fluorescence emission), and non-radiative degeneration (dissipated as heat). Intramolecular rotation restriction prevents non-radiative decay and makes it easier for brilliant emission to occur in the aggregation stage. On the contrary, the PTT effect got elevated as the result of heat released by the aggregation-induced emission (AIE) molecules.

Likewise, in a biological environment, more intramolecular communication in donor-acceptor (D-A) based coplanar NIR particles has obstructed all thermal intensity discharge pathways. Subsequently, controlling atomic movement in the collected state is one method for adjusting both heat intensity generation and emission for broadened accuracy in the analysis and exhaustion of cancer growths. In the making of novel photothermal treatment, researchers proved that boron quantum dots have shown potential for the treatment of growths [78]. These unique compounds exhibit great photoacoustic imaging performance, and are biocompatible, and are thought to be non-toxic. The safety of BQDs was established in vitro, and in vivo research demonstrated their potent photothermal conversion effect and photothermal ablative capability. It is safe to assume that these innovative formulations could provide a solid platform for upcoming cancer therapy research and development.

#### **8. Photo dynamic therapy**

Photodynamic treatment is an arising and promising helpful methodology for fighting a loathsome illness like malignant growth [79, 80]. Photodynamic treatment is a treatment methodology that joins the photophysical and photochemical cycles to achieve natural impact [81]. Photodynamic treatment utilizes natural photosensitizers that, when presented to light, produce singlet oxygen. QDs have broadly been utilized for this reason, and specialists have created water-dissolvable nanocomposites in view of CdSe/ZnS QDs and hydrophobic tetraphenylporphyrin particles passivated by chitosan. These nanocomposites showed a 45% typical productivity in creating singlet oxygen due to the intracomplex Förster reverberation energy move with TPP.

It incorporates the actual course of photochemically responding to an energized photosensitizer with either cell substrates or sub-atomic oxygen, which at last outcomes in the passing of disease cells. The photosensitizer has two electrons with contradicting spins in a low-energy sub-atomic orbital in its ground state. One of these electrons is excited to higher energy atomic orbitals without changing spins when light is ingested [82]. Because of the photodrug's concise lifetime in this state, which is known as the singlet excited state, it cannot take part in responses with cell substrates (going from nano to picoseconds).

The excited photosensitizer can either go through fluorescence, which delivers light energy, to get back to its ground state, or non-radiative decay, which delivers heat energy through inward conversion (IC). The improvement of photosensitizers from the original to the ongoing third era, delivery systems, the development or suppression of immunity, combinational treatment, and other basic components of photodynamic treatment should be in every way completely talked about. The utilization of late made quantum dots is growing in photodynamic treatment (PDT). The primary benefits of utilizing these QDs are that they beat the downsides of conventional PDT compounds through having great photostability, high quantum yield, areas of strength for and as a result of their huge change dipole moment [83, 84].

Moreover, the photophysical qualities and fluid solvency of the core can be custom fitted to address specific issues by shifting their size and content, which offers a huge surface region for linkage to biomolecules like peptides and antibodies. Be that as it may, the results of QDs utilized freely in photodynamic treatment (PDT) were disappointing. They can notwithstanding, participate in fluorescence reverberation energy move (FRET) by filling in as energy benefactors, which various gatherings effectively utilized for PDT. The FRET interaction is shown by the contributor particles'

#### *Application of Quantum Dots in Bio-Sensing, Bio-Imaging, Drug Delivery, Anti-Bacterial… DOI: http://dx.doi.org/10.5772/intechopen.107018*

extinguished fluorescence and the acceptor atoms' expanded fluorescence. QDs alone are not effective at creating singlet oxygen, however, when joined with normal dyes, the combination produces singlet oxygen with a high quantum yield. Their closeness, estimated in nanometers, is the principal essential for FRET from QD to PS. They can remain joined by noncovalent complexes or covalent bonds. The problem of QD instability in biological media has been addressed by a variety of surface modification techniques. Commonly, amphiphilic molecules are used to encase QDs. The hydrophobic cavity of the QD is encircled by the hydrophobic end of the molecule, which permits the QD to disperse in solution. This is a widely used encapsulation method because it addresses the issues of luminescence quantum yields and colloidal stability [85].

The size of the particle will determine whether or not effective QDs can be developed for diagnostic and therapeutic uses. A QD can pass through biological barriers like the alveolo-capillary, blood-brain barrier, gastric, and barriers in the dermis as well as the renal filtration barrier if its core material has a minimum diameter of 8–10 nm (which is typically increased with surface features) [86]. Before commercializing QDs for use in humans, we must conduct additional research on their potential toxicity, which will take time overall [87]. According to a recent study, the creation of noble carbon dots from curcumin and folic acid improved the effectiveness of photodynamic therapy in treating cancer cells. For nucleus-targeting PDT, conjugated carbon dots (CCDs), a novel two-photon active photosensitizer was proved to release lethal reactive oxygen species (ROS). Through a pathway mediated by folate-receptor, a combination of carbon dots, curcumin, and folic acid (CDcf) was discovered to interact with malignant cells, leading to significant localization within the nucleus. PDT efficiency eventually increased as a result of the increased reactive oxygen species (ROS) generation in the nucleus brought on by two-photon excitation. As a result, by directly attacking cancer cells' DNA, cancer cells were eliminated more successfully. The development of multi-functional dual-photon active nanoformulation on a solo stage for improved PDT in oral malignancy diagnosis and therapy was made possible by CDs' inherent ROS generation and nucleus-targeting capacity. In order to aim and distribute PDT proxies accurately and efficiently, CDcf has developed a new approach. Furthermore, the technique can be easily expanded for better enactment in the nanoprobes with added malignant cell lines using targeted therapy and diagnosis [88].

## **9. Quantum dots in optoelectronic devices**

Optoelectronic systems are very interested in quantum dots because of their unique characteristics [89, 90]. A new generation of semiconductor devices known as quantum dots has been the focus of the nanotechnology sector. Due to their ability to provide special properties, quantum dots, also known as "artificial atoms," are now being used in a variety of high-performance devices. They have improved the performance of solar cells and lasers, for example. The adequacy and usefulness of these promising nanomaterials for cutting-edge optoelectronic gadgets in both modern and biomedical fields have been further developed through various endeavors made around the world [91]. Lasers, photo-detectors (photodiode), amplifiers, and solar cells are a few examples of optoelectronic devices. Researchers have developed quantum dot devices over the past two decades that outperform earlier devices based on quantum dots in terms of performance. Self-assembled nanoparticles have drawn a lot of attention for many years. A semiconductor can develop specific unique properties by reducing its size to the nanoscale. Nanometer-sized semiconductors

can have their electrical and optical properties altered by manipulating their morphology. Similar to electrons, semiconductor quantum dots (QDs) are an intriguing nanoscale structure of confined carriers in all dimensions [92]. Zero-dimensional semiconductor nanostructures are more tunable and delicate to outer boundaries than customary mass semiconductors; furthermore, in light of the fact that QDs are zerodimensional, their energy levels can be dense to an assortment of delta functions. The key advantages of low-layered semiconductors have produced a lot of interest. Early research established the wavelength tunability and threshold reduction capabilities of quantum-organized semiconductor lasers, which were subsequently theoretically supported. Since there was not a practical method for making QDs for several years after these groundbreaking studies, efforts to develop QDs and use them in devices were limited to experimental research. Quickly following the effective production of self-assembled quantum dot laser diodes (QD based 77 K operational diodes) were created [93, 94]. A worldwide drive was begun to further develop quantum dots development control after an exhibit of self-collected quantum dots and the main quantum dot laser. Indium arsenide/indium phosphide (InAs/InP) and gallium arsenide (In(Ga)As/GaAs) [92] are two instances of mismatched grids that definitely stand out from researchers [95]. Heteroepitaxial development modes in thin films are regularly made sense by utilizing thermodynamic justifications. Further developed QD self-gathering got prompt prizes. Lasers, as well as quantum dab enhancers, quantum dot solar cells (QDSCs), quantum dot infrared photodetectors (QDIPs), and quantum dot super-luminescent diodes (QDSLDs), have all been accounted for [96]. Between subband assimilation in QDs in the last part of the 1990s prompted the advancement of mid-frequency and long-frequency infra-red photo-detectors. Selfcoordinated quantum dots optoelectronic gadgets have progressed essentially since these nanostructures were first created [97].

In terms of efficiency, quantum dot lasers are now on par with quantum well lasers. Inter-sublevel instruments have improved efficiency and unique properties, and they can be used as light sources and detectors. Future systems are predicted to heavily rely on quantum dot optoelectronic sensors. Additionally, high-performance QDIPs are made possible by active research in QDs [98]. The fact that QDIPs can operate at higher temperatures and have lower dark currents gives them a fundamental advantage over QWIPs. Efficiency of quantum-well IR photo-detectors (QWIPs) has been surpassed by QD-IR photo-detectors (QDIPs) [99]. Moreover, there are as yet various issues, including deficient quantum execution and the requirement for further developed QDIP engineering and creation to completely use their true capacity in third-age infrared detecting [100]. In the impending years, QDIPs with effectiveness tantamount to present state-of-the-art advancements like QWIPs and HgCdTe photodetector might be utilized [101]. Quantum wells are less developed than quantum dots (QDs) to the extent that optoelectronic systems plan on account of different head imperfections in QDs' slow retention and the very thermal relationship between the intermediate and conduction band [102]. To accomplish high transformation productivity far in excess of the record worth of GaAs single-intersection solar cells, extra improvements in gadget physical science, plan, development, and portrayal of QDSCs would be required [103, 104]. QD-based biosensors are widely used in science, engineering, and technology to monitor many facets of contemporary life. To advance research in these fields, it is necessary to comprehend the various types of sensors, how to use them for different applications, as well as how to optimize and utilize them. Quantum dots (QDs), which are zero-dimensional semiconductors, exhibit optical gain, laser technology, strong light absorption, and

#### *Application of Quantum Dots in Bio-Sensing, Bio-Imaging, Drug Delivery, Anti-Bacterial… DOI: http://dx.doi.org/10.5772/intechopen.107018*

intense narrow-band radiation over the visible and infrared bands. Imaging, solar energy deriving, display units, and signal transportation can all benefit from these qualities. One of the modest light-emitting technologies is the use of LECs (lightemitting electrochemical cells). Numerous LECs have been confirmed by means of a variety of biological materials, including fluorescent polymers. The understanding of LECs using materials of inorganic form, predominantly materials of low-dimensional is interesting to relate to light-emitting diodes/instruments, that have been made possible by recent advances in this QD device technologies. Recent developments in two-dimensional and low-dimensional materials, like chiral light-emitting devices and materials based on quantum dots, offer significant functionalities that hold promise for new optoelectronic applications based on emergent materials [105].

#### **10. Challenges and future perspectives**

Even though QDs have an extensive choice of applications, including in vivo biomedical imaging and detection, they also have the potential to be harmful to both human health and the environment. Typically, QDs can impair organism function and cause metabolic disability or death through at least three distinct pathways. The QDs' composition comes first and is of utmost importance [106]. Toxic ions could be released from QDs and poison cells during internal corrosion. As the nanoparticles have a high surface-to-volume ratio, they are more prospective than bulk material to undergo partial decomposition and release ions [107–109]. Regardless of composition, QDs' small size creates another potential drawback because particles can adhere to cell membranes or be ingested and retained inside cells, impairing organ function. It was discovered that many QDs have toxic effects, with earlier studies attributing the cause to the presence of hazardous metals. Commercial quantum dots frequently contain the toxic heavy metal core CDs cadmium, lead, mercury, and arsenic [110, 111]. According to reports, the Cd-core QDs were indeed cytotoxic, particularly when surface oxidation from air or UV exposure caused reduced Cd to form on the particle surface and the release of free Cd2+ ions. The cells were damaged after being cultured with CdSe QDs for seven days, showing diffused nuclei and ill-defined cell boundaries [112, 113]. Additionally, it was demonstrated that cadmium telluride (CdTe) QDs had negative effects on cellular functions, with the smaller ones emitting green light is more harmful than the larger ones emitting red light [114]. In imaging, clinical applications, and basic biomedical research, QDs hold great promise. To comprehend the potential of these new generation materials, a review of QD properties and general perception is conducted. The toxicity of these nanoparticles is one significant barrier, but it is not yet fully understood. Before commercializing QDs for use in humans, we must conduct additional research on their potential toxicity, which will take time overall [105, 115–118].

#### **11. Summary and conclusion**

Numerous implications for celllabelling, biomedical imaging, diagnostics, and drug delivery are provided by quantum dots. They have benefits over traditional fluorescent dyes and green fluorescence proteins, including a size similar to antibodies that enables combined applications using these recognition molecules, narrow-emission and broad-excitation spectra, high intense photons, and anti-quenching ability,

wavelength tunability making them suitable for multi-wavelength applications, and high brightness and photostability. Quantum dots might not be able to replace all of the other fluorophores currently employed in labeling and imaging, though. In addition to their excellent photophysical characteristics, quantum dots face some difficulties, such as restricted in vivo applications due to complex surface chemistry. Quantum dots are frequently used in conjunction with other kinds of fluorophores to great effect. They may be advantageous in some applications but disadvantageous in others. QDs must be small enough to penetrate biological barriers if they are to be used in routine clinical settings for diagnostic and therapeutic purposes. Additionally, they must have low toxicities. The theranostic applications of QDs-based biosensors are covered in detail in this chapter. Although there are opposing views on QDs' biocompatibility and toxicity, they have made significant strides in the field of research thus far. The most recent article was published a few years ago, and now scientists are starting to realize how QDs can be used for therapeutic, diagnostic, and sensing purposes. Despite all of this, creating smart formulations using QDs still presents a number of difficulties.
