Folate-AuNP—Folate-gold nanoparticles, MTX-AuNP—Methotrexate-gold nanoparticles, VCR-AuNP— Vincristine-gold nanoparticles, 6MP-AuNP—6-Mercaptopurine-gold nanoparticles, 5-FU-Glutathione-AuNP— 5-Flourouracil-gold nanoparticles, αHFR—Alpha human folate receptor. with permission from reference [106]. Types of Nanoparticles Drugs/Payloads Applications/Outcomes

#### *3.6. Mesoporous Silica Nanoparticles (MSNs)* Magnetic MSNs #-

Due to their extraordinary potential as nanocarriers for cancer therapy and imaging, mesoporous silica nanoparticles have received the attention of researchers [89–94]. MSNs have been studied and found to be promising carriers for biomedical imaging and drug delivery due to their good biocompatibility, high pore volume, uniform pore size distribution, large surface area and further chemical modification on the surface of MSNs to modulate the nanoparticle surface characteristics. Furthermore, pharmaceuticals can be placed onto the mesoporous, resulting in prolonged drug release [94,95]. Mesoporous sizes range from 2 to 50 nm. MCM-41 nanoparticles were the most extensively described MSNs for cancer therapy. This class of MSN is hexagonally structured homogeneous mesoporous that facilitates drugs to be loaded into micro-channels while also inhibiting the pre-release of loaded drugs [2,96]. On surfaces of the amine groups of MSNs, polyethylene glycol was conjugated to create long-circulation MSNs [97]. The Schematic representation of multifunctional mesoporous silica nanoparticles are shown in Figure 7. Neutrophils carrying Doxorubicin Precise diagnosis and high anti-glioma efficacy MSNs- Poly-L-histidine and PEG coated Sorafenib Improved cancer therapy by PH trigger drug release MSNs-CuS #- Nanodots coated Doxorubicin Imaging and synergetic chemo-photothermal effect MSNs-PEGylated lipid bilayer coating Axitinib, celastrol Improved cancer therapy Organo MSNS-Polyethyleneimine coated Doxorubicin P-gp SiRNA # Preventing multi drug resistance and promotion of chemotherapy # MSNs—Mesoporous silica nanoparticles, MSNs-CuS—Mesoporous silica nanoparticles-copper sulfide, P-gp—P-glycoprotein, SiRNA—Small interfering RNA.

Figure 7. Schematic representation of multifunctional mesoporous silica nanoparticles. **Figure 7.** Schematic representation of multifunctional mesoporous silica nanoparticles.

3.7. Superparamagnetic Iron Oxide Nanoparticlesd (SPIONs) 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. For tumour cell targeting, several targeting ligands such as transferrin, mannose and folic acid (FA) have been coupled on surfaces of the MSNs. For example, the folate receptor (FR), which is typically overexpressed in many human tumour cells, has been widely employed in targeting the tumour cells and nanomaterial treatment. Researchers used an amide linkage to conjugate folate with polyethyleneimine and then this co-polymer coated with silica particles. When compared to non-targeted nanoparticles, FA-modified

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

tions. 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 rep-

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

resentation of multifunctional SPIONs are shown in Figure 8.

silica nanoparticles showed increased cytotoxicity in both human cervical and breast cancer cells and tumour absorption [98–100]. MSNs are employed in nucleic acid-guided treatments and nucleic acid delivery because of their relatively large surface area, superior biocompatibility for functionalization and variable pore size used to encapsulate various cargos [101–104].

MSNs have recently been developed as nanocarriers for photodynamic therapy (PDT), photothermal therapy (PTT), or both. PTT and PDT, two important types of phototherapies, sparked a lot of interest in various cancer treatments [105]. The applications of MSNs are shown in Table 6.

**Table 6.** Applications of MSNs using cancer models for improved cancer therapy. Reproduced with permission from reference [106].

