Nanorobotics sometimes is referred to as molecular robotics, an emerging technology field dealing with the design, simulation, control and others at or near the scale of a nanometer (Ghosh and Fischer
2009). The terms nanobot, nanomachince, nanowire or nanomite have also been used to describe such devices currently under research or development (Hoop
et al.
2018; Soto
et al.
2020; Yarin
2010). Intelligence nanorobots here are recognized as nanomachines that can perform controlled and adjustable stimuli-triggered response automatically regarding to different physiological environments or that can achieve some specific or special functions in physiological processes. Using nanomchines to perform precise tasks in the human body is seen as the frontier in nanomedicine (Unciti-Broceta
2015). Bioorthogonal catalysis provides new ways of mediating artificial transformations in living systems (Unciti-Broceta
2015). Combined with bioorthogonal reactions, intelligence nanorobots are endowed with more preponderance (Hoop
et al.
2018). Nanozymes with the ability to regulate catalytic activity through chemical and physical signals can provide a biomimetic and dynamic control of bioorthogonal reactions (Wang
et al.
2019). Wang
et al. developed a first-in-class nanobot, a family of gold nanoparticles (AuNPs) encapsulating hydrophobic TMCs including Ru and Pd catalysts which can control their catalytic activity through a supramolecular host-guest strategy (Wang
et al.
2019). Actually, the authors have employed the host-guest molecular recognition strategy to hide toxicity of gold nuclear with the help of CB[7] in 2010, the toxic AuNP-NH
2 would be liberated when the competitive ADA was added to exert its effect. Combining with bioorthogonal reaction, the new devices were designed on basis of 2-nm AuNPs, featuring a hydrophobic alkane segment, a tetra (ethylene glycol) unit and a dimethylbenzylammonium group (Fig. 1D), which are functionalized to bind with cucurit[7]uril (CB[7]) through host-guest chemistry as well (Tonga
et al.
2015; Unciti-Broceta
2015). The complexation of nanozymes with CB[7] in this system blocks the access of substrates to the catalytic site, resulting in the complete inhibition of catalytic activity. However, this inhibition was reversible after the addition of 1-adamantylamine (ADA), a competing guest molecule, removing CB[7] away and allowing substrate access to catalytic sites (Fig. 1A) (Tonga
et al.
2015; Wang
et al.
2019). Using the catalyst, substrate was transformed into luminous or curative product, identifying the function of this strategy. This kind of nanorobot using supramolecular gated-activation system has been applied to living systems, such as intracellular prodrug activation in Hela cells (Fig. 1B) (Tonga
et al.
2015). The release of catalyst could be intelligently controlled by addition of ADA, but the catalyst can’t be recycled after being freed. Asier Unciti-Broceta proposed that soft spring linkers could be used as confinement of catalyst (Unciti-Broceta
2015). When the host-guest system is applied into living bodies, selectivity and stability should be considered as well to avoid the side effect of drugs or catalysts.