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the combined therapy compared to treatment with individual drug-conjugated nanocarriers or free drug suspensions (Fig. 10).

CNTs can also be coupled to other nanosystems with this purpose, such as magnetic particles, quantum dots, nanocomposites, etc. Zhang et al. [193] functionalized magnetofuorescent MWCNTs for MRI/fuorescence imaging by adding a Gd complex doped with quantum dots. They also combined the nanotubes with doxorubicin to be used as a chemotherapeutic agent. The nanotubes were intratumorally injected in a preclinical model of adenocarcinoma, and visualized with photoacoustic imaging and magnetic resonance T1-weighted images. Using NIR absorption properties, the authors carried out photothermal therapy in combination with selective release of DOX in the tumor. In a similar way, Hou et al. [194] functionalized SWCNTs with HA, DOX, and gadolinium to visualize with MRI the biodistribution of the nanotubes and their antitumor e ect in a preclinical model of breast cancer.

CNTs can also be used as theranostic dual contrast agents for fuorescence/MRI and photothermal therapy, all in a system [195]. The authors So, Zhang, and colleagues reported the preparation of and in vitro and in vivo characterization of MWCNT-magnetofuorescent carbon quantum dots/DOX nanocomposites. They validated the diagnostic and therapeutic capacities of the compounds with MRI and fuorescent methodologies in adenocarcinoma cells and a pulmonary cancer mouse model. The study confirmed that the platform is able to target cancer cells and deliver drugs intracellularly upon NIR irradiation, achieving the e ective elimination of the tumors through chemo/photothermal synergistic therapeutic e ect. In a similar way, Xiaojing Wang et al. [196] described the synthesis of modified DNASWCNTs with gold-decorated nanoparticles and a surface modification with PEG, which achieve the selective photothermal ablation of cancer cells. These SWNT-Au- PEG nanocomposites are optical theranostic probes for cancer treatment by PPT and detectable by Raman spectroscopic imaging. Another study, carried out by Zhao and coworkers [197], reports the coating of CNTs with polydopamine and further modification by PEG to chelate manganese, achieving contrast in MRI, and to label 131I enabling nuclear imaging and radioisotope cancer therapy. The system was tested in vitro and in a mouse model of breast cancer, assessing radioisotope therapy in combination with NIR-triggered photothermal treatment. Results revealed e cient tumor accumulation of the nanotubes and confirmed a remarkable synergistic antitumor therapeutic e ect.

4.4  Tissue Engineering Applications

The main clue in regeneration and construction of tissues is the development of a suitable biological sca old. In this context, owing to their unique characteristics and properties, carbon nanotubes are emerging as smart nanomaterials for tissue engineering purposes. They are valued as ideal structures that can support and boost the growth and proliferation of many di erent tissues [15].

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4.4.1  CNTs and Cell Growing

Nanobiotechnology can have a great impact in the management of nervous system pathologies by developing optimal structures for neural prosthetic applications. The design of biocompatible implants for neuron repair/regeneration ideally requires high cell adhesion as well as good electrical conductivity. Carbon nanotubes entail all of these requirements, including high binding a nity and excellent electrical conductivity, making them ideal materials for neuro-implant development aimed to grow neurons and repair neuronal damage. Some examples have already presented in earlier. Lovan et al. [198] showed that carbon nanotubes possess a good surface for supporting dendrite elongation and cell adhesion. Experiments were carried out on neonatal hippocampal neuron networks cultured on dispersed MWCNTs. Results suggested that the growth of neuronal circuits on a nanotube grid is accompanied by a significant increase in network activity, probably due to the high electrical conductivity of these nanomaterials. In the same line, Mazzatenta et al. [199] described the preparation of an integrated SWCNT–neuron system by growing hippocampal cells on the CNTs. Theoretical and experimental results indicated that SWCNTs can stimulate the activity of the brain circuits.

However, CNT applications in tissue regeneration or engineering expand far beyond nervous tissue. Ren et al. [200] used CNTs to develop artificial myocardial tissue where cell growth was aided by the conductivity of oriented CNTs. Special nanotube geometry also beneficiated artificial bone generation, making CNTs a very suitable bone sca old both in vitro and in vivo [201, 202]. Finally, CNTs make an important contribution in the generation of synthetic fiber muscle [203, 204].

4.4.2 CNT-Based Hydrogels

Although conventional hydrogels are biocompatible and suitable for culturing or fabricating di erent cell types and tissues, their low mechanical strength and lack of electrical conductivity have limited their biomedical applications for skeletal muscles, cardiac and neural cells. Nevertheless, the development of hybrid nanocomposite systems can overcome these limitations enabling the preparation of biosca olds with tunable electrical and mechanical features. In fact, in the last few years, CNTbased hybrid hydrogels are emerging as innovative candidates with applications in regenerative medicine and tissue engineering [205]. Shin et al. [206] prepared different nanotube–hydrogel hybrid systems that showed significantly improved electrophysiological and mechanical properties. The authors seeded neonatal rat cardiomyocytes onto these hybrid MWCNTs hydrogels, obtaining functional cardiac patches that showed excellent mechanical integrity and advanced electrophysiological functions. Another study reports the addition of functionalized MWCNTs to alginate to generate composite hydrogels improving the mechanical, physical, and biological features compared with the starting materials [207]. The obtained hybrid MWCNT–alginate gels were porous, showed less degradation, enhanced HeLa cells adhesion and had greater cell proliferation, proving the potential utility of these structures as novel substrates for tissue preparation. Sun et al. [208] incorporated SWCNTs into collagen hydrogels, which improved cell alignment and assembly,

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