PAMAM dendrimer—Poly(amidoamine) dendrimer, PAMAM-PEG dendrimer—Poly(amidoamine) poly(ethylene glycol), PPI-dendrimer—Poly(propylene imine) dendrimers, RNA—Ribonucleic acid.

#### *3.3. Micelles*

Polymeric micelles have gained popularity in recent years and have become one of the most well-studied nanocarriers in cancer detection and treatment. These micelles are made up of spherically shaped, self-assembled amphiphilic block co-polymers with a hydrophilic corona and the hydrophobic core in an aqueous medium with a diameter ranging from 10–100 nm. Hydrophobic drugs can be accommodated in the core of the micelle [54,55]. In active targeting of tumour cells, several kinds of ligands, such as aptamers, peptides, antibodies, carbohydrates, folic acid, etc., are utilized to decorate the micelle surface. The stimuli-based micelle drug delivery systems are based on enzymes, ultrasound, temperature changes, PH gradient and oxidation [56]. To enhance intracellular uptake, a variety of functional groups can be attached to the micelle's hydrophilic end. The active components of the pH-sensitive polymeric micelle are generally released at lower pH [57]. The co-delivery technique, which employs a multifunctional micelle, is critical for the synergistic benefits in tumour therapies. The temperature-stimuli micelle-based co-delivery system described by Seo et al. is capable of transporting genetics as well as anti-tumour medications [58]. Polyion complex (PIC) micelles are a type of micelle that is being researched primarily for the efficient delivery of genes and siRNAs [59]. The schematic representation of multifunctional micelles as shown in Figure 4. Molecules 2022, 27, x FOR PEER REVIEW 8 of 27

> in cancer therapy. CNTs are produced from graphene sheets rolled into a seamless cylinder with a high aspect ratio, diameters as small as 1 nm and their lengths can reach up to several micrometres and they can be open-ended or capped [63]. The two types of carbon nanotubes are single-walled carbon nanotube (SWCNTs) and multi-walled carbon nanotubes (MWCNTS). Single-walled carbon nanotubes are single graphene cylinders, whereas multi-walled carbon nanotubes are a complex nesting of graphene cylinders. SWCNTs have a smaller diameter, are more flexible and can help with imaging. On the other hand, MWCNT's have a large surface area and so the endohedral filling is more efficient [64–66]. Carbon nanotubes received more attention among other carbon-based nanocarriers and spherical nanoparticles due to their distinctive properties such as intracellular bioavailability, high cargo loading and ultra-high aspect ratio [67,68]. The sche-

> CNTs have been utilized in a variety of applications, including anticancer drug delivery and gene therapy. Non-spherical nanocarriers like carbon nanotubes can stay in lymph nodes for longer than spherical nanocarriers like liposomes [63]. According to Yang et al., CNTs could be utilised to target lymph node tumours. In this study, FA-functionalized MWCNTs were used to entrap magnetic nanoparticles incorporated with cisplatin. The nanotubes were dragged to the lymph nodes using an external magnet and the drug release was achieved for several days in the tumour cells [69,70]. To make CNTs smart, they should be functionalized chemically or physically [71]. PEGylation is a critical

> Another area of research that is now being investigated is the use of functionalized carbon nanotubes as a nanocarrier for gene therapy. Biomolecules such as miRNA, siRNA, dsDNA and others, in comparison to small molecule drugs, cannot enter cellular membranes and are quickly breakdown by nucleases [68,73]. On the surfaces of carbon nanotubes both RNA and DNA can easily accommodate, improve the therapeutic efficacy of aptamers, micro-RNA (miRNAs) and small interference RNA (siRNAs), oligonucleotides and double-stranded DNA (dsDNA) and because of their extraordinary flexibility and structure, carbon nanotubes can also carry large amounts of genetic materials to targeted areas [74,75]. The different types of CNTs used for cancer therapy are shown in Table 4. In the treatment of cancer, immunotherapy may be an alternative to gene therapy. SWNTs were coated with tumour-specific fluorescent probe, radiometal ion chelates and monoclonal antibodies. A variety of approaches have been shown to be capable of targeting the

Figure 4. Schematic representation of multifunctional micelles. **Figure 4.** Schematic representation of multifunctional micelles.

3.4. Carbon Nanotubes (CNTs)

tumour (lymphoma) [76].

matic representation of multifunctional CNTs are shown in Figure 5.

step in increasing solubility, avoiding RES and reducing toxicity [72].

Wan et al. conducted a study of designer polymeric micelles for targeting ovarian and breast cancers, which featured simultaneous loading of paclitaxel and cisplatin in amphiphilic copolymer-based micelles, which resulted in a considerable increase in loading efficiencies [60]. P-glycoprotein (P-gp) is an efflux transporter, The efflux of diffused intracellular anticancer medicines is mostly caused by overexpression of P-gp in tumour cells, resulting in low bioavailability of the drug. Razzaq, S et al. developed a mucopermeating papain functionalized thiolated redox micelle for site-specific administration of paclitaxel, that the developed formulations can inhibit P-gp efflux pump, improve oral bioavailability, higher penetration and enhanced efficacy compared to conventional paclitaxel formulation [61]. The different types of polymeric micelle for cancer therapy used in clinical trials are shown in Table 3.

**Table 3.** Polymeric micelle for cancer therapy in clinical trial or uses. Reproduced with permission from reference [62].

