MSNs—Mesoporous silica nanoparticles, MSNs-CuS—Mesoporous silica nanoparticles-copper sulfide, P-gp— P-glycoprotein, SiRNA—Small interfering RNA. these targeting moieties, resulting in dose reduction and off-target effects [115]. The SPI-ONs used or under clinical trials for cancer therapy are shown in Table 7.

#### *3.7. Superparamagnetic Iron Oxide Nanoparticlesd (SPIONs)* Table 7. Superparamagnetic iron oxide nanoparticles (SPIONs) in use or under clinical trials for

SPIONs have become one of the most intensively investigated targeted nanomaterials because of their exceptional super-paramagnetic capabilities, which allow them to aggregate in a specific tissue under an external magnetic field [107]. When exposed to an alternating magnetic field (AMF), SPIONs have excellent magnetic resonance imaging (MRI), photothermal and magnetic heating capabilities, as well as strong biocompatibility. All of these characteristics make them promising candidates for use as a drug delivery system, a contrast agent in MRI and a thermotherapy agent [108,109]. SPIONs, on the other hand, have limited use since they agglomerate and are not stable in aqueous solutions. The constraint could be overcome by covering the SPION surface with various materials to change its surface properties [110]. The optimal size of nanoparticles in drug delivery systems based on SPIONs for in vivo applications should be between 10 and 200 nm, which allows them to avoid extravasation and renal clearance (<10 nm) and escape the attack of reticuloendothelial system macrophages (>200 nm) [111]. The schematic representation of multifunctional SPIONs are shown in Figure 8. cancer therapy. Reproduced with permission from reference [116]. S. N. Product Name Formulation Status Application 1 Gastromark® Aqueous suspension of silicone coated SPIONs FDA-approved Magnetic resonance imaging 2 Feridex® SPIONs coated with dextran FDA-approved Magnetic resonance imaging 3 Feraheme® SPIONs coated with polyglucose sorbitol carboxymethylether FDA-approved Magnetic resonance imaging 4 NCT01270139 Iron bearing nanoparticles Clinical trial Hyperthermia 5 NCT01436123 Gold nanoparticles with iron oxide-silica shells Clinical trial Hyperthermia

ities by nature. With the proper modifications, QDs are water-soluble and can be produced in sizes like 2–4 nm [117]. This nanocarrier could be utilised to visualise the tumour while the drug is being delivered to the desired location. A core, a shell and a capping substance are the three parts of commercially available QDs. A semiconductor material, such as CdSe, is used for the core. The semiconductor core is surrounded by a shell made of another semiconductor, such as ZnS. The double-layer QDs made of various substances are encapsulated by a cap [118]. In physiological systems the performance of quantum dots can be improved by functionalizing with biocompatible polymeric materials (PEG) or biological targeting molecules (antibodies) on the surfaces of quantum dots [119–122]. Graphene quantum dots (GQD), carbon quantum dots (CQD) and cadmium-based QDs are the most often used QDs. Cadmium derivatives, like cadmium sulphide (CdS) and cadmium selenide (CdSe), are the most often utilised for core materials. These systems have been thoroughly investigated in terms of toxicity, size, photoluminescence, morphology, biocompatibility and stability [123]. Substances such as telluride and sele-

Figure 8. Schematic representation of multifunctional SPIONs. **Figure 8.** Schematic representation of multifunctional SPIONs.

3.8. Quantum Dots (QDs)

Polymers, liposomes, inorganic nanoparticles and viral vectors, including adenoviruses, have typically been conjugated with SPIONs. Surface modification of SPIONs has recently resulted in remarkable development in the field of magnetic nanoparticle-based nonviral medication delivery systems [112,113]. Such systems can deposit in the tumour region via superparamagnetic SPION capabilities in the presence of an external magnetic field (active) or by the enhanced permeability and retention effect (passive) [114]. Conjugation of SPION-based drug delivery systems with targeting moieties such as antibodies, hyaluronic acid, transferrin, peptides, folate and targeting aptamers (e.g., Arg-Gly Asp (RGD)) provides an alternate technique for improving targeting performance. Certain integrins/receptors that are overexpressed on the tumour cell surface can be detected by these targeting moieties, resulting in dose reduction and off-target effects [115]. The SPIONs used or under clinical trials for cancer therapy are shown in Table 7.


**Table 7.** Superparamagnetic iron oxide nanoparticles (SPIONs) in use or under clinical trials for cancer therapy. Reproduced with permission from reference [116].

## *3.8. Quantum Dots (QDs)*

QDs are inorganic nanoparticles that have electrical, optical and fluorescent capabilities by nature. With the proper modifications, QDs are water-soluble and can be produced in sizes like 2–4 nm [117]. This nanocarrier could be utilised to visualise the tumour while the drug is being delivered to the desired location. A core, a shell and a capping substance are the three parts of commercially available QDs. A semiconductor material, such as CdSe, is used for the core. The semiconductor core is surrounded by a shell made of another semiconductor, such as ZnS. The double-layer QDs made of various substances are encapsulated by a cap [118]. In physiological systems the performance of quantum dots can be improved by functionalizing with biocompatible polymeric materials (PEG) or biological targeting molecules (antibodies) on the surfaces of quantum dots [119–122].

Graphene quantum dots (GQD), carbon quantum dots (CQD) and cadmium-based QDs are the most often used QDs. Cadmium derivatives, like cadmium sulphide (CdS) and cadmium selenide (CdSe), are the most often utilised for core materials. These systems have been thoroughly investigated in terms of toxicity, size, photoluminescence, morphology, biocompatibility and stability [123]. Substances such as telluride and selenium give the system semiconductor and optical characteristics, making QDs semiconducting [124]. The usage of graphene-based QDs in targeting tumour cells and imaging has increased due to overcoming the cadmium-related toxicity problems. G-QDs can be further modified to increase their targeting towards a certain tumour cell type, making them more appealing for cancer subtype mapping and site-specific imaging [125]. Carbon QDs are the new types of nanostructures with the ability to replace conventional dots due to superior features such as photo-stability and biocompatibility [126,127]. The schematic representation of multifunctional quantum dots is shown in Figure 9.

Figure 9. Schematic representation of multifunctional quantum dots. **Figure 9.** Schematic representation of multifunctional quantum dots.

4. Types of Targeting Moieties Various targeting moieties are used for targeted delivery in cancer therapy, target moieties are commonly incorporated on surfaces of transporters by physical absorption or chemical reaction. Peptides, proteins, nucleic acids and small molecules (carbohydrates or vitamins) are examples of targeting moieties. The researchers created a novel formulation that includes graphene quantum dots conjugated with mesoporous silica nanoparticles (MSN) to provide a synergistic chemophotothermal treatment. The GQD-MSN-DOX combination's particle size was estimated to be between 50 and 60 nm. It also demonstrated temperature and pH-dependent drug release, as well as photothermal therapy generated by near-infrared irradiation, resulting in the formation of heat to destroy the malignant cells. This technology has also proven to be biocompatible and absorbed by 4T1 breast tumour cells. Chemo-photothermal therapy's synergistic impact appears to be an excellent technique for cancer targeted therapy [128]. The applications of QDs are shown in Table 8.

nium give the system semiconductor and optical characteristics, making QDs semiconducting [124]. The usage of graphene-based QDs in targeting tumour cells and imaging has increased due to overcoming the cadmium-related toxicity problems. G-QDs can be further modified to increase their targeting towards a certain tumour cell type, making them more appealing for cancer subtype mapping and site-specific imaging [125]. Carbon QDs are the new types of nanostructures with the ability to replace conventional dots due to superior features such as photo-stability and biocompatibility [126,127]. The schematic

The researchers created a novel formulation that includes graphene quantum dots conjugated with mesoporous silica nanoparticles (MSN) to provide a synergistic chemophotothermal treatment. The GQD-MSN-DOX combination's particle size was estimated to be between 50 and 60 nm. It also demonstrated temperature and pH-dependent drug release, as well as photothermal therapy generated by near-infrared irradiation, resulting in the formation of heat to destroy the malignant cells. This technology has also proven to be biocompatible and absorbed by 4T1 breast tumour cells. Chemo-photothermal therapy's synergistic impact appears to be an excellent technique for cancer targeted therapy

Table 8. Applications of QDs in drug delivery for augmented cancer therapy. Reproduced with

Liver cancer

Cancer theragnostic

Combination of PTT #

PH dependent release + Photothermal therapy

tor for cancer therapy

and PDT #

S. N. Delivery System Purpose

4 Nitrogen functionalized GQD-methotrexate Breast cancer

5 GQD-Biotin-Doxorubicin Targeting overexpressed biotin recep-

 GQD—Graphene quantum dots, GQD-DOX—Graphene quantum dots-Doxorubicin, QDs-PEG— Quantum dots-polyethylene glycol, PTT—Photothermal therapy, PDT—Photodynamic therapy.

representation of multifunctional quantum dots is shown in Figure 9.

[128]. The applications of QDs are shown in Table 8.

2 GQD-mesoporous silica nanoparticle-DOX #

permission from reference [129].

#

1 Zinc oxide QDs #

3 Silicon dioxide -GQD-DOX #

6 Black phosphorous QDs-PEG #

**Table 8.** Applications of QDs in drug delivery for augmented cancer therapy. Reproduced with permission from reference [129].

