## 3 Application of Nanotechnology in Stem-Cell Therapy
### Nanotechnology Application for Monitoring Stem-Cell Therapy Progress
In vivo, ultrasmall superparamagnetic iron oxide (USPIO)-PHO could mark amyloid plaques in the NMRI mice brain; anti-A\(\beta\) protein precursor (A\(\beta\)PP) antibody-conjugated SPIONs can visualize the number of plaques in A\(\beta\)PP/PS1 transgenic mice. DDNP-SPIONs nanoparticles significantly decrease the signal intensity (SI) in the hippocampal area in the rat AD model. Curcumin-conjugated superparamagnetic iron oxides (SPIOs) can detect amyloid plaques in Tg2576 mice brains. Fibrin \(\gamma\)377–395 peptide-conjugated-Fe\({}_{2}\)O\({}_{3}\) nanoparticles could specifically inhibit the microglial cells in rTg4510 tau-mutant mice and thus provide a possible therapeutic strategy towards neurodegenerative tauopathies. In addition, magnetic IONPs bound to an anti-ferritin antibody were developed to detect ferritin protein in areas with a high amount of amyloid plaques in the brain of a transgenic AD mouse model. BBB, blood–brain barrier. Adapted with some modification from [72], [PERSON] et al., 2020. Currently, developing techniques such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and near-infrared (NIR) fluorophores offer noninvasive models for tracking transplanted stem cells. Among these techniques, MRI by high spatial resolution is an ideal tool to gain high quality cellular and molecular images and is used in tracking engrafted stem cells in treatment of brain diseases. Treating the implanted cell with an intracellular contrast agent provides visualization of MSCs using MRI. Combination of PET with MRI can render useful information regarding cell tracking, optimal cell dose and graft volume. SPECT is a nuclear tomographic imaging technique equipped with a gamma ray camera. In a cell-transplanted brain of a PD model, activity of dopaminergic compounds was measured by SPECT-[1231] ultrapane. Near-infrared light (NIR) is another noninvasive imaging tool with ability of penetrating deep into tissues. To define the precise location of implanted hMSCs, NIR scanner was used to provide 3D images contain the contour, reconstruction and coronal section at cell-engrafted site of hMSCs [76]. Nanotechnology has beneficial for improve efficiency of these techniques in localization of transplanted stem cells. The magnetic properties of metallic NPs make them useful for magnetic resonance imaging. Loading stem cells with AuNPs can facilitate tracking of transplanted cells in stem-cell therapy procedures. Complexation of 40-nm AuNPs with two ligands, poly L-lysine (PLL) and rhodamine B isothicarate (RITC) improved NPs uptake by human mesenchymal stem cells, without inhibition of cell proliferation or differentiation [77]. Carbon quantum dots (CQDs) are also ideal tools for tracking transplanted cells. Covering mesenchymal stem cells with CQDs prior to implantation into the sciatic nerves allowed their tracking for at least 35 days, in vivo [78]. Some specifically developed lipid-base NPs like liposomes are able to treat neurodegenerative diseases and can be promising candidates for integrated treatment with stem-cell therapies. Conjugation of liposomes with apolipoprotein E (ApoE) increased delivery of siRNA or plasmid DNA to the brain, result in improving target liposomes to neural stem and progenitor cells [79]. Paramagnetic compounds such as SPIO-NPs are commonly used contrast agents. Recently, research has been carried out to evaluate the effects of SPIO-uptake on the in vitro activity of hMSCs and as a consequence, the effect of SPIO concentration on MRI sensitivity. Outputs of these studies revealed that during generation of high contrast MRI signals, SPIO-uptake would not have negative effects on the proliferation or differentiation processes. Implantation of SPIO-tagged MSCs in experimental models lead to high resolution MRI, supporting the beneficial behavior of SPIO labeling for stable MRI tracing [80].