*4.2. Carbon Nanotubes*

As mentioned above, there are two types of CNTs, namely, SWNTs and MWNTs. SWNTs have strong optical absorption in the visible and NIR regions due to the optical properties of CNTs, such as resonance. Raman-scattering and photoluminescence in the near IR region make CNTs useful for biomedical imaging. SWNTs exhibit di fferent optical absorption peaks from the UV region to the near IR region, which made these NPs suitable for utilization as photo-thermal agents and photo-acoustic imaging agents [99] (Figure 9).

Liu et al. [100] have reported how in vivo integrin αvβ3 imaging was able to utilize SWNTs and SWNTs functionalized by PEG-ylated phospholipids to increase water solubility which was labelled by a 64-Cu radioisotope for micro PET imaging. RGD peptide conjugated 64 Cu radiated SWNTs to PEG coating (SWNT-PEG 5400-RGD) was injected intravenously into the glioblastoma U87MG tumor in mice and then monitored by a micro PET. The results demonstrated higher uptake of SWNT-PRG5400-RGD by the tumor (~13% of dose ID/g) when compared to the tumor uptake of SWNTs without combination with RGD (4~5%) of injected dose per gram tissue. Moreover, Smith et al. [97] have used RGD conjugated with PEG-ylated SWNTs as a Raman nanoprobe for in vivo tumor imaging in mice, where SWNT-RGD was injected intravenously into the mice's tumors with high integrin αvβ3 expression. Raman microscopy showed strong signals for tumor cells injected with SWNT RGD while weak signals were recorded for the tumors injected with non-targeted SWNTs. They also utilized SWNT-RGD as a contrast agen<sup>t</sup> for tumor photoacoustic imaging. PET imaging and Raman imaging showed strong photoacoustic signals in U87MG tumors. CNTs with their impressive biocompatibility have demonstrated grea<sup>t</sup> success in the imaging field, thus encouraging scientists to explore their applicability in the diagnosis of most common diseases other than cancer. Nevertheless, CNTs have not been explored widely owing due to their di fficult and expensive preparation methods.

**Figure 9.** A single-walled carbon nanotube and an aqueous solution of SWNTs functionalized by PEG-SWNTs with highly optical properties, which are considered excellent platforms for biomedical imaging [99]. Reproduced with copyright permission from Springer Nature, 2010.

### *4.3. Super Paramagnetic Iron Oxides NPs*

Superparamagnetic iron oxide (SPIO) NPs have been widely utilized as a contrast agen<sup>t</sup> in MRI imaging; FeCo alloys have the best magnetic properties but because of oxidation and toxicity their appearance in biomedical applications has been limited [101]. Iron-based oxide NPs have been investigated by Won et al. [95], in which coated FeCo nanocrystals with a single layer of graphite carbon (GC) was used as a contrast agen<sup>t</sup> for MRI. These NPs were PEG-ylated to increase the solubility of the FeCo/GC NPs. The water-soluble FeCo/GC NPs exhibited higher relaxivities on a per metal atom basis compared to other materials which utilized MRI as a contrast agent. Afsaneh et al. [102] have reported on recently developed MRI and PET imaging probes using SPIO NPs as a contrast agen<sup>t</sup> where iron oxide NPs were coated with various coats, such as poly aspartic acid, PEG, dopamine, and dextran. The e ffects of these coats were discussed with regards to the particle size, targeted organ, final uptake, and time retention in the studied organ.

One of the methods by which magnetic NPs are delivered to the diseased organ is by intravenous infusion or by means of a blood circulatory system. Another method relies on utilizing magnetic nanoparticles suspensions for infusion. A steady uniform solution is required to avoid the aggregation of the NPs. Particle size and surface functionalization are two parameters required for the stability of the magnetic colloidal suspension. Determination of appropriate magnetic nanoparticles is the principal significant advancement for bioapplication. For applications in drug delivery, the magnetic nanoparticles are required to be steady in water at neutral pH, which relies on their size, charge, and surface functionalization. However, super magnetic materials, for example, cobalt and nickel, are not utilized in biomedical applications because of their lethal properties and oxidation susceptibility.

## *4.4. Gold NPs*

Gold NPs have been highlighted among contrast agen<sup>t</sup> materials for their bioimaging application. Monodispersity, stability, and higher attenuation coe fficients for X-rays are the impressive properties which make these NPs suitable for this process. Peng et al. [91] have found that a way to synthesize dendrimer-stabilized gold NPs is by use of amine-terminated fifth-generation poly(amidoamine) (PAMAM) dendrimers. These were modified by diatrizoic acid as stabilizers for enhanced CT imaging. Li et al. [103] prepared Au-coated iron oxide (Fe3O4-Au) nanoroses to be used as a probe for multi-function as well as aptamer-based targeting, MRI, optical imaging, photo thermal therapy, and chemotherapy. Zhang et al. [104] prepared PEG with PEI-stabilized gold NPs for blood pool, lymph node, and tumor CT imaging. Moreover, Yigit et al. [105] synthesized gold NPs conjugated to 3,3-diethylthiatricarbocyanine iodide (AuNP-DTTC) which is used as a contrast agen<sup>t</sup> for in vivo MRI and Raman spectroscopy. Here the probe consisted of MRI-active super paramagnetic iron oxide NPs coupled with AuNP-DTTC. Tailoring the properties of gold NPs and utilizing chemical techniques has grown extensively in the last two decades, especially in the field of bio-imaging. Developed tests and probing techniques rely on advances in gold nanoparticles conjugates, new optically-controlled functional materials, new highly specific color-coded probes of cellular function, and new optically-based therapeutic methods.

## **5. Porous Membranes**

The second objective of this review is to present an overview of the therapeutic applications of porous membranes and their key challenges. Porous membranes have been used in numerous engineering applications such as molecular separation, catalysis, and filtration, etc. [106,107]. Literature shows that porous membranes are frequently regarded as nanoporous structures because the pore size of such membranes lies between 1 and 100 nm, although several terminologies have been used to explain these porous membranes and the terms nanoporous and microporous are used based on pore size [108,109]. In this section, di fferent types of membranes, types of materials, etched membranes, and the fabrication of micro- and nanoporous membranes are briefly explained (Figure 10). In the following sections, the properties, surface modification techniques, biocompatibility, and drug delivery applications are also discussed. Lastly, we describe the key challenges and future prospects of these membranes.

**Figure 10.** Key characteristics of porous membranes.
