**3. Application of porphyrins and hemeproteins in the construction and working of micro-/nanorobots**

#### **3.1 Porphyrins and derivatives**

Several studies have been developed to produce nanodevices containing porphyrins with a potential use in MNRs to be applied in theranostics. According to Li et al. [83], porphyrins have a diversity of properties applicable to health preservation, diagnosis, and treatment. Porphyrins can amplify signals for magnetic resonance imaging (MRI), positron emission tomography (PET), infrared fluorescence imaging, and dual modal PET-MRI. Porphyrins have chemical and physical properties that allow the application of these compounds in the detection and destruction of tumors. Porphyrins can efficiently convert light into electronic excitation of molecular oxygen to produce singlet oxygen in photodynamic therapy (PDT) or light to heat for photothermal therapy (PTT). Therefore, porphyrins have been applied in the treatment of solid cancers and ocular vascularization diseases [29]. Also, there are some studies about porphyrin-nanoparticle systems employed in dentistry treatment [84–87]. These systems can be used in the diagnosis of cancer by acting, for instance, as biosensors that exhibit affinity for a single molecule converting biochemical to electrical signals, detection of salivary biomarkers of oral tumors, and others [85, 88]. The capacity of self-assembly in a range of supramolecular aggregates is a crucial property for the application of porphyrins to construct MNRs [29, 89]. Ion et al. [89] demonstrated that porphyrins could self-assemble in several types of supramolecular aggregates such as linear head to tail, J-aggregates, and fractal aggregates with diverse and definite photophysical properties (**Figure 6**) [89].

The study of Ion et al. showed nanotubes formed by porphyrins and the importance of this technique for brain aneurysm instrumentation. They used meso-5, 10, 15, 20-sulfonate-phenyl porphyrin (TPPS4) and observed the formation of organized nanostructures by ionic self-assembly. Neurons and glial cells incubated with porphyrin nanotubes formed interconnected networks featured on the nanotube templates. The capacity of TPPS4 to form nanotubes by self-assembly demonstrates the potential of this porphyrin in the fabrication of NMRs applied to medicine. MNRs must have the capacity to self-propel that could be provided by a diversity of materials and mechanisms. Park et al. describe the fabrication of "swimmers": microstructures with autonomous mobility at water/air interface. The particles of porphyrin-based

**Figure 6.**

*Supramolecular aggregates of meso-5,10,15,20-sulfonate-phenyl porphyrin (TPPS4). (a) The free-base monomer of TPPS4, (b) the head-to-tail linear self-assembly of TPPS4, and (c) the J-aggregate of TPPS4.*

metal–organic frameworks (MOFs) were fabricated with hydrophobic meso-tetra (4-carboxyphenyl)-porphyrin (H4-TCPP-H2, L) ligands bound to Zr-oxo clusters. The H4-TCPP-H2, L responds for the hydrophobic character of the framework [90]. Similar MOFs were described in the literature before, once they are efficient in the controlled release of surface-active substances proportionating a controlled motion. However, usually, the MOFs use high-cost surface-active substances [90]. The MOFs fabricated with meso-tetra(4-carboxyphenyl)-porphyrin ligands bound to Zr-oxo clusters use much less expensive fuels. The particles have the advantage to be refueled multiple times and attained speeds of ca. 200 mm·s<sup>−</sup><sup>1</sup> . Interestingly, the type of fuel, the microstructure, and surface wettability of the MOF surface determine the efficiency of motion. In another study, Serrà et al. [91] reported the fabrication of a multifunctional nanorobotic platform with magnetic properties to promote the death of cancer cells by magnetic and mechanical destruction. A multi-segmented nanowire composed by nickel and gold alternating segments was produced by electrodeposition of metals inside the nanochannels of a polycarbonate membrane. In sequence, the nickel segments were transformed in core-shell Ni/NiO segments by the treatment of the nanowire with NaOH 0.5 M for 6 h. The nanowires were treated sequentially with zinc protoporphyrin IX and 1,9-nonanedithiol that displaces the porphyrin from the gold segments. The nanotubes exhibited ferromagnetism and could be manipulated by a magnet. When the bi-functionalized nanotubes attain cells, magnet or photostimulation can induce cell death that is useful for cancer treatments since the effect of some medical procedures, like hyperthermia and photodynamic therapy, could be improved by application of a rotary magnetic field [91].
