This simple, reproducible, and solvent-free approach is based on the joint fusion of CD and typically a carbonyl linker, being diphenyl carbonate the most used. In general, the homogenization occurs at 90–130°C during at least 5 h, to ensure a complete crosslinking reaction (Sadjadi et al., 2019b; Iriventi et al., 2020). For further crosslinking, the mixture must be incubated for a longer period (Rezaei et al., 2021). At the end of the reaction a fine homogeneous powder is obtained (Jasim et al., 2020; Moin et al., 2020; Sadjadi and Koohestani, 2021a, 2021b; Srivastava et al., 2021). The powdered substance is repeatedly washed with water and/or acetone, and, generally, it is also subjected to Soxhlet extraction with ethanol or acetone, and even to an additional washing with sodium hydroxide (NaOH) solution (Kumar A. and Rao R., 2021; Sadjadi and Koohestani, 2021a, 2021b; Suvarna et al., 2021). Water allows the removal of CD in excess and ethanol/acetone allows the elimination of the unreacted crosslinker and still other impurities such as phenol or imidazole, formed when DPC or CDI linkers are used, respectively. Typically, the phenoxide ion formed from phenol is soluble in water, so the rinse with a base (NaOH) will ensure the total removal of this impurity, which can be observed using a ferric salt (Garrido et al., 2019; Kumar et al., 2021), UV-vis spectroscopy or HPLC (Sadjadi et al., 2018c).

This strategy involves dissolving CD and a crosslinker in an appropriate solvent, namely, petroleum-based polar aprotic solvents such as DMF, DMSO, butanone or pyridine (Anandam and Selvamuthukumar, 2014), or green solvents to make the process more sustainable, such as water or aqueous solutions (Swaminathan et al., 2010a; Jafari Nasab et al., 2018) and deep natural eutectic solvents (NADES) (Cecone et al., 2020). If necessary, a catalyst can be added to reduce reaction time (Demasi et al., 2021). Typically, an excess of crosslinking agent is used in CD:crosslinker molar ratios in the range of 1:2 to 1:16 (Jain et al., 2020). In general, after the reaction, the recovery of NSs may involve precipitation using water, acetone (Khajeh Dangolani et al., 2019) or ethyl acetate (Cecone et al., 2018, 2019; Matencio et al., 2020b) among other possible solvents (Ferro et al., 2014; Appell et al., 2018; Garrido et al., 2019; Lo Meo et al., 2020; Pawar and Shende, 2021).

In the case of using dianhydride linkers alone or with 2-hydroxyethyl disulphide (Daga et al., 2016), the addition of triethylamine (Et₃N) as basic catalyst is required, and the exothermic reaction occurs quickly at room temperature (Nazerdeylami et al., 2021; Suvarna et al., 2021; Yazdani et al., 2021). Using other linkers, such as HDI (Yazdani et al., 2021), MDI (Khajeh Dangolani et al., 2019), DMC and DPC (Singh et al., 2018), Et₃N can also be introduced to increase the rate of the reaction, with or without an increase in temperature. Furthermore, the use of another base, 1,4-diazabicyclo(2,2,2)octane (DABCO), was reported to catalyse the reaction involving BDE as crosslinker in aqueous NaOH solution at 90°C or to catalyse the process using HDI and βCD at r. t. (Ramírez-Ambrosi et al., 2014). Basic conditions (NaOH) are also required for the reticulation of CD with EPI (Olteanu et al., 2014; Jafari Nasab et al., 2018; Liu X. et al., 2020). Other bases such as ammonia, pyridine and collidine can be used as catalysts as well (Trotta, 2011). According to the literature, when CA is chosen as linker, the reaction takes place under vacuum in water and at a temperature equal to or above its normal boiling point (Varan et al., 2020; Rubin Pedrazzo et al., 2022) or in NADES, such as a choline chloride/CA mixture, which acts both as solvent and co-reactant (Cecone et al., 2020). Sometimes, the addition of sodium hypophosphite monohydrate as catalyst is also required with this linker. Another example of this method involves the reaction between βCD and NDCA crosslinker, in aqueous media and using sulfuric acid as catalyst, to obtain the corresponding CDNSs after 2 days at 100°C (Nait Bachir et al., 2019).

This method involves the complete dissolution of the CD in an alkaline aqueous phase, pH > 10, and the crosslinking agent in an organic one (methylene chloride, butanone or chloroform) (Shende P. et al., 2015; Desai and Shende, 2021).

Based on the phenomenon of emulsification, this process consists of two immiscible phases: one internal and one external. The internal phase is formed when the crosslinker is added dropwise, under constant magnetic stirring, to a solution containing CD and an inclusion analyte in a polar aprotic solvent (usually DMF). The external phase is an aqueous solution to which the internal phase is then added drop by drop, under vigorous stirring, at room temperature. The suspension obtained is lyophilized and the CDNSs are subsequently dried (Gangadharappa et al., 2017).

Through the application of ultrasonic vibration, it is possible to promote crosslinking of CD with an appropriate linker, in a certain molar ratio, and in the absence of solvents, thus constituting an environmentally friendly process. Spherical uniform size particles are formed (Ciesielska et al., 2020; Jain et al., 2020; Omar et al., 2020). The sonication is useful either for the melting or for the solvent condensation method (Swaminathan et al., 2013).

Conventional and ultrasound heating methods lead to non-uniform transformations due to the occurrence of thermal gradients and, consequently, to longer reaction times and scalability problems. As such, the promotion of reactions by microwave irradiation makes them four times faster than the melting approach (Andaç et al., 2021), and more reproducible and scalable due to uniform and controlled heating provided by microwave irradiation. Thus, using microwave synthesis, it is possible to obtain highly crystalline CDNSs with a narrow particle size distribution (Ciesielska et al., 2020) by reacting CD with an appropriate crosslinker (mostly DPC), using polar aprotic solvents such as DMF (Anandam and Selvamuthukumar, 2014; Zainuddin et al., 2017; Sharma et al., 2021). As the solvent condensation synthesis can be performed using microwave irradiation, Vasconcelos et al. (Vasconcelos et al., 2016) reported the use of tin octanoate catalyst to promote the reaction between βCD and HDI crosslinker using DMF as solvent in a microwave system at 80°C for 30 min.

CD-crosslinker reaction can also be induced by mechanochemistry (Jicsinszky and Cravotto, 2021), the direct absorption of mechanical energy, capable of activating chemical bonds. Usually, this type of activation occurs between solids or solidified reactants in ball mills, in the absence of solvents or minimizing their use as much as possible, contrary to what happens conventionally, whereby a large quantity of solvents, mostly derived from fossil fuels, are used. So, mechanosynthesis is a more sustainable method, where mass transport and energy dispersion are guaranteed through efficient grinding in the solid state. Although solvents such as acetone and ethanol continue to be used in CDNSs’ purification, they are relatively volatile, in contrast with high boiling point polar aprotic solvents (DMSO or DMF), that have complex recycling processes. The use of ball mills has disadvantages such as difficult scalability, the impossibility of precise temperature control (although it does not exceed 72°C in CDNSs’ synthesis), and the use of closed containers that increase the polycondensation reaction time due to the impossibility of water removal during these batch processes. These drawbacks can be overcome by using twin-screw extruder reactors, which allow not only a tight temperature control but also makes processes more scalable by transitioning from a batch approach to a continuous process. In general, mechanosynthesis is a simple, economical, and faster strategy for obtaining CDNSs. Two examples are: 1) the use of ball mills to obtain CDNSs using CDI as cross-linker in 3 h; and 2) the use of said extruder for the preparation of CDNSs using βCD, CA crosslinker, and sodium hypophosphite monohydrate as catalyst. In the latter case, the equipment is preheated to a temperature between 120 and 180°C and the solid blend is slowly inserted into it and the process lasts between 5 and 25 min, contrary to the conventional approach that takes place in vacuum for at least 4 h, using water as solvent (Rubin Pedrazzo et al., 2020, 2022; Trotta and Pedrazzo, 2020).

The conventional step growth procedures are based on a polycondensation reaction in which monomers react with each other and, subsequently, a new monomer reacts with the polymer under construction, presenting both functional groups with identical reactivity. However, it is possible to evolve to a chain-growth polycondensation method, in the case of the reactive group at the polymer chain’s end, formed by reaction with the monomer, is stable and more reactive than the monomer itself (Yokozawa and Ohta, 2016). Thus, an initiator can be used to promote polymer growth by creating points of high reactivity at its tip, so that the binding of a new monomer readily occurs, and so on, in these reactive ends, allowing the increase of the chain. CDNSs with reduced polydispersity are obtained, as the monomers do not interact with each other, but selectively connect with the reactive terminals. A chain-growth approach reported by Khalid et al. (Khalid et al., 2021) is based on the use of βCD together with acrylic acid monomer in the presence of ammonium persulfate as initiator and MBA as crosslinking agent.

Heavy metals constitute one of the major classes of pollutant worldwide because of their easy absorption by living organisms leading to bioaugmentation and bioaccumulation. Particularly, the exposure to heavy metals can produce allergic reactions, mental disability, dementia, vision problem as well as liver and kidney diseases (Vareda et al., 2016) (Vareda et al., 2019).

CDNSs prepared by using either aliphatic or aromatic crosslinkers for the removal of a broad range of heavy metals (e.g., Cu(II), Zn(II), Pb(II), Cd(II), Ni(II), Co(II), Hg(II), Fe(III), and Cr(III), and As(V)) have been synthesised and tested. Table 4 summarizes the most relevant data on the NSs and sorption parameters.

Concerning aliphatic-based CDNSs, citric acid (Rubin Pedrazzo et al., 2019) and EDTA (Zhao et al., 2015) are relevant crosslinkers, not only because they form highly crosslinked materials but also due to the number of available carboxylic acid groups, which allows a significant increase in active sites for interaction with metal ions. Moreover, the sorption ability of these materials is pH responsive. βCD:EDTA shows the highest removal efficiency for Cd(II) and Cu(II) reaching values higher than 90% (Zhao et al., 2015).

A different approach is the modification of chitosan by EDTA, followed by the crosslinking to βCD using pentafluoropyridine (βCD‒PFP‒CTS/EDTA). This βCD‒PFP‒CTS/EDTA NS exploits the simultaneous chelating ability of CTS and EDTA. As for pure βCD‒EDTA, the sorption process is promoted at acidic pH with a removal higher than 90% for Pb(II), Ni(II), Cu(II), Co(II), Hg(II) and Cr(III) in about 1 min (Yu et al., 2018b). Likewise, the removal of Pb(II), Cu(II) and Cd(II) was studied by using NSs of βCD and TFP and methacrylic-βCD with 1‒vinylimidazole (VI) (MCD:VI). βCD:TFP exhibits the largest active surface area which plays a key role on the significant amount of heavy metals sorbed per gram of material (Pb(II): 196.4 mg g⁻¹, Cu(II): 164.4 mg g⁻¹ and Cd(II): 136.4 mg g⁻¹). However, its removal efficiency diminishes along cycles of sorption/desorption (He et al., 2017). The pH responsive MCD:VI adsorbent was synthesized at different molar ratios. At 1:100 mol/mol, it has revealed the best sorbent performance for Pb(II), Cu(II), Cd(II), Zn(II), Ni(II) and Co(II). The sorption ability of MCD:VI via coordinative interaction decreases in the order Cd(II)>Cu(II)>Zn(II)>Ni(II)>Co(II)>Pb(II) within 70–15 mg g⁻¹ (Qin et al., 2019). Moreover, βCD crosslinked with pyromellitic dianhydride (βCD:PMA) was tested for Cu(II), Zn(II), Pb(II), Cd(II) and Fe(III) removal and the results were compared to those obtained for βCD:CA. Both materials show similar removal efficiencies (from 20 to 70%), however, the highest removal efficiencies (ca. 80%) are obtained for initial low concentrations of Cu(II) and Zn(II) (Rubin Pedrazzo et al., 2019).

Toluene diisocyanate was used to synthesize βCD and (6‒deoxy)‒(6‒benzylimidazolium)‒βCD NSs. The latter shows higher efficiency in the removal of metal ions, due to electrostatic interactions and chelating ability of the imidazolium groups, as well as higher thermal stability (Raoov et al., 2014). The hydroxyl-rich tannic acid (TA) is an interesting monomer used to synthesise βCD-TA nanosponge crosslinked by terephthaloyl chloride (TPC) and applied for Pb(II) removal. βCD:TPC:TA shows a selective and high removal efficiency of 97% for Pb(II) at alkaline pH, in the presence of salt, humic acid and other interferents (Yang et al., 2022).

Dyes are used in many industries, mainly involving the production of consumables, including textiles, inks and paper. The textile industry is one of the activities that consumes greatest amounts of water, either in quality or in quantity, associated with the use of dyes, which makes this industry one of the biggest water body pollutants. Moreover, dyes are, in general, water soluble compounds, making them difficult to remove from wastewaters (Lellis et al., 2019). Being a relevant issue, several CDNSs have shown effectiveness in removing dyes (Table 5). For instance, βCD:EPI macroparticles show a spontaneous and exothermic sorption of DirectBlue78 (Murcia-Salvador et al., 2019). The effect of other cyclodextrins, αCD and hydroxypropyl-αCD, on the synthesis of NSs and consequent performance on Direct Red83:1 dye removal has been evaluated. The removal efficiency (RE) and the maximum amount sorbed (q _m ) of RE = 92.8% and q _m = 31.5 mg g⁻¹ and RE = 75% and q _m = 23.41 mg g⁻¹, for αCD:EPI and HP-αCD:EPI, respectively, have been obtained (Pellicer et al., 2018).

The βCD:EDTA was also applied for the removal of different dyes (methylene blue (MB), safranin O (SF) and crystal violet (CV)), highlighting the removal efficiency higher than 90% for the MB. As mentioned above, the presence of carboxylate groups in EDTA are relevant for the interaction with dye molecules (Zhao et al., 2015).

On the other hand, MCD:VI obtained via free radical copolymerization at different molar ratios (from 1:10 to 1:150 mol/mol) was tested for sorption of rhodamine B (RB) and Congo red (CR); it has been demonstrated that pH strongly influences the electrostatic and π‒π interactions occurring between NSs and dye molecules. Moreover the affinity of dyes towards MCD depends on the VI molar ratio; i.e., for CR the q _m increases by increasing the molar ratio, reaching a maximum q _m value (1.12 mg g⁻¹) for MCD:VI150 and for RB, the opposite is observed (the highest q _m value is obtained for MCD:VI10, 336 mg g⁻¹) (Qin et al., 2019).

The effect of benzyl-βCD hyperlinked with 4,4′-bipyridine (PD), synthesised through the Menshutkin reaction, in the sorption of two cationic (RB and MB) and two anionic (CR and methyl orange, MO) dyes has been reported by Li et al. This NS is effective in the removal of anionic dyes: RE = 80 and 77% for CR and MO, respectively (Li X. et al., 2018).

MB is a molecule used very often as a drug and dye model. Therefore, the interaction between MB and NS goes beyond the interest in the sorption of MB onto NSs. The copolymerization of two molecules containing cavity gates [the βCD and the pillar (5)arene (P5)], using TFP as crosslinker, provides the ability to form two different types of host‒guest complexes as well as to manage the hydrophilic/hydrophobic balance of the NS. Lu et al. (Lu et al., 2019) have found that by increasing the molar fraction of P5 the hydrophobicity increases and the best removal efficiency of MB is attained (78%).

Different classes of dye intermediates and dyes derived from benzene were studied using two uncommon linkers: the 4,4′‒difluorodiphenylsulfone (FPS) and the 4,4′-bis(chloromethyl)-1,1′-biphenyl (CMP) for βCD and βBCD, respectively. βCD:FPS was tested for 2-naphthol removal allowing >80 and 99% removal efficiency for in batch and in flow-through sorption experiments, respectively (Wang et al., 2017). On the other hand, the adsorption of different aromatic compounds, such as nitrobenzene, 2-nitrophenol, 2-nitroaniline, 4-nitroaniline and 2‒chloroaniline, onto βCD:CMP has also been evaluated. It is worth mentioning that, for this NS, the percentage of crosslinker significantly modifies the active surface area; i.e., an increase in the crosslinking degree may result in an increase in the surface area up to 5 times. Thus, surface area and the phenyls groups play a crucial role on the sorption efficiency by enhancing the π‒π interactions with removal efficiency >70% for any dye intermediates (Huang et al., 2020).

Nowadays pesticides are one of the most concerning classes of substances related with environmental pollution and human health issues. Recently, nanosponges have been considered promising sorbent materials and they were applied for removal of pesticides and their intermediates such as, atrazine, benalaxyl, bromacil, butachlor, butylene fipronil, fenamiphos, fipronil, fluprifole, fomesafen, pretilachlor, simazine, 4‒n‒nonylphenol (4nNP), 4‒n‒octylphenol (4nOP) and 4‒tert‒octyphenol (4tOP) (Table 6).

Macroparticles of αCD:EPI, βCD:EPI and γCD:EPI, with diameter ranging from 0.212 to 0.250 mm, were used for atrazine sorption. αCD:EPI and βCD:EPI have similar removal efficiencies (around 60%) with sorption isotherms characterized by the Freundlich model, whilst the RE of γCD:EPI is only 50%, in agreement with the highest ratio between the volume of γCD cavity and the aromatic ring of atrazine (Romita et al., 2019). Additionally, atrazine, benalaxyl, bromacil, butachlor, butylene fipronil, fenamiphos, fipronil, fomesafen, pretilachlor and simazine were tested in a screening study of sorption ability of βCD:EPI, γCD:EPI, HPβCD:EPI, randomly methylated βCD:EPI (RM-βCD:EPI), equimolar mixture of β-γ-CD:EPI, βHPβCD:EPI and γHPβCD:EPI and a physical mixture of βCD:EPI, HPβCD:EPI and RM-βCD:EPI with mass ratio of 40:30:30 (w/w) (multiplex). Multiplex NSs combining the physico‒chemical properties of the three materials, show the best performance as sorbent material, even at low concentrations either in deionized water or in sea water, even after five cycles of regeneration (Liu et al., 2011). In a similar way βCD:EPI and γCD:EPI were initially synthesised and, subsequently, oxidized with KMnO₄. Albeit swelling ratio, particle and pore sizes, the crosslinking degree and hydrophilicity increase by increasing the amount of KMnO₄, while the CD content and surface area decrease concomitantly. It has also be found that γCD:EPI is more efficient for hydrophobic compound removal (i.e. benalaxyl, butachlor, fipronil and flufiprole) whereas βCD:EPI performs better for hydrophilic pesticides (i.e. atrazine, bromacil, fenamiphos, pretilachlor) (Wang M. et al., 2021). The sorption experiments involving 4nNP, 4nOP and 4tOP and CD-based:EPI NSs, where the mixture of α- β- and γCD NS, using EPI as crosslinker, stands out, have shown high removal efficiencies for all the adsorbates. In general, all sorbents have RE around 90%. However, the HP-βCD shows the highest performance, in the order 4tOP>4nNP≈4nOP, due to its higher hydrophilicity and host‒guest complex formation (Crini et al., 2021).

In a recent study, βCDNSs were synthesized using as linker two diamine monomers: 1,6‒hexane diamine and 1,12‒dodecane diamine. Physico‒chemical properties were characterized and their influence on the sorption process assessed. Both materials present similar particle size (430 nm) but the CD-am₆ shows lower thermal stability but higher hydrophilicity, surface area and pore size. These properties seem to have relevance for the highest removal efficiency of imidacloprid (>90%), obtained for initial concentrations of IMD ranging from 20 to 300 mg L⁻¹ (Utzeri et al., 2022). On the other hand, for βCD crosslinked with hexamethylene diisocyanate (βCD:HDI) the removal efficiencies for imidacloprid and cymoxanil were low; however, by forming composite gels with just 10% (w/w) of AC the removal efficiency increases to 81 and 73%, respectively (Utzeri et al., 2021).

Spherical βCD:HDI (10 equivalents of crosslinker) with high thermal stability was applied for the removal of 2,4‒dinitrophenol (2,4NP) in different environmental water samples (tap water, lake water, river water and sea water). A higher removal efficiency (ca. 74%), at acidic pH and low analyte concentration, was observed; the RE remained constant along five sorption/desorption cycles (Anne et al., 2018). In the same study, the performance of βCD:TDI for the removal of 2,4NP has been compared with that obtained by using βCD:HDI. The porous βCD:TDI presents higher efficiency (ca. 85%) than the non-porous βCD:HDI. However, results can also be justified by considering the presence of the phenyl groups of the linkers, which can form π‒π interactions with 2,4-dichlorophenoxy acid (2,4D) (Anne et al., 2018).

As was pointed out in the previous section, β-BZMCD:TDI was applied for the removal of a set of phenols with different substitutions. The β-BZMCD:TDI shows higher ability than the non-substituted βCD:TDI, with an average removal percentage equal to 85%, which can be justified by its higher porosity (Raoov et al., 2014). The sorption of 2,4CP onto βCD:TTI (triphenylmethane‒4,4′,4″‒trisocyanate), synthesised using 2‒butanone as solvent, has been studied. The properties of the NS is highly affected by the catalyst/linker ratio, temperature and βCD:TTI molar ratio (Zhou L. et al., 2019). Another example of a common aromatic linker is TFP. A study comparing the sorbent performance of porous and non-porous βCD:TFP has also been reported. Sorption tests were performed with 2,4CP, 1-naphtyl amine and metolachlor. Porous βCD:TFP has a lower water uptake, compared with non-porous material, but has shown better removal efficiency ≥85% (Alsbaiee et al., 2016). Pure βCD:TFP was also used as control material in comparison with a mixture of two monomers, TFP and 5,5′,6,6′‒tetrahydroxy-3,3,3′,3′-tetramethylspirobisindande (THTS), prepared in dimethylacetamide. Overall, NS particles exhibit dimensions ca. 90 nm diameter with micro‒ and meso‒pores and higher active surface area; these properties are improved by increasing the THTS percentage. The βCD:TFP:THTS0.5 is the most efficient material for various micropollutants. Particularly, it sorbs 460 mg g⁻¹ of 2,4CP per gram of sorbent corresponding to around 90% of removal efficiency. βCD:P5 at molar ratio 1:1 presents the best hydrophilic behaviour, higher surface area (479 m² g⁻¹) than βCD:TFP and larger pore size (3.5 nm) than P5:TFP. They represent an advantage on sorption processes of 1‒naphthylamine with removal efficiency of around 80% in aqueous solution and environmental conditions (Lu et al., 2019). An interesting study reported by Klemes et al. shows how solvent, catalyst (K₂CO₃) and crosslinker ratio influence both reaction yield and physico‒chemical properties of βCD:TFP NS. Higher TFP amount led to a decrease in reaction yield and phenolate incorporation. Moreover, depending on the method of addition of K₂CO₃, a porous material may result, with 346 m² g⁻¹ of active surface, or even a non‒porous material. NSs obtained using different methods were tested towards 83 pesticides. In general, a stronger affinity of the micropollutants was observed for the porous βCD:TFP synthesised by using DMSO, with higher surface area and phenolate content (Klemes et al., 2018). Another extensive study involving βCD:TFP, was carried out by Li et al. (Li C. et al., 2018). It has been demonstrated that for almost all pesticides the removal efficiency of the NS is higher than 70%.

NSs based on aromatic linkers such as FPS, CMP and DPC have also been prepared and their performance towards pesticide sorption evaluated. The sorption of 2,4CP by βCD:FPS (1:2 mol/mol) showed a removal efficiency higher than 80% (Wang et al., 2017). The aromatic crosslinker can act synergetically in the sorption process of organic adsorbates; for example, the sorption of 2NP, 2,4CP, 2,6CP and 2,4,6CP onto βCD:CMP increases by increasing the amount of crosslinker (Huang et al., 2020).

The incorporation of Fe₃O₄ nanoparticles into βCD:DPC for the sorption of aromatic chlorinated pesticides [4‒chlorophenoxyacetic acid (CPA) and 2,3,4,6‒tetrachlorophenol (TCP)] has demonstrated that no variation of removal efficiency occurs; however, the sorption kinetics seem to be facilitated by the presence of NPs (Salazar et al., 2018). The same research group has also tested this composite for dinotefuran removal with similar results (Salazar et al., 2020).

Non‒porous materials with high thermal stability were synthesized using BDE as linker for α-, β- and γCDs. The materials were mainly applied for ciprofloxacin removal, although they were also tested for carbendazim (a broad-spectrum fungicide) with 70% of active substance sorbed in 30 min and a value of 90% can be reached after 5 h sorption (Rizzi et al., 2021).

Hybrid NSs, which include CD and a polymer, have also been synthesised and tested for the removal of pesticides. Recently, poly (vinyl alcohol)-βCD has been synthesised and its adsorption performance evaluated towards paraquat. The obtained material shows a very fast adsorption of pesticide, with a RE of around 96% in just 3 min, following a Langmuir mechanism (Martwong et al., 2021, 2022).

As the other classes of pollutants, pharmaceuticals represent one of the biggest concern in relation with ecosystem pollution and its side effects. In Europe, they were detected in surface and groundwater that are used in agriculture and drinking water production. Thus, strategical actions are made to face this issue. One of these strategies is the development of efficient sorbent materials, including nanosponges (Table 7). βCD:EPI particles were employed in a pilot scale test for the simultaneous removal of eight different drugs (β‒estradiol, ethynyl estradiol, estriol, ibuprofen, diclofenac, naproxen, ketoprofen and cholesterol) from greenhouse municipal wastewater. Particles reach up ca. 99% of removal efficiency for hormones and 85% for ibuprofen and diclofenac, in‒flow sorption process (Fenyvesi et al., 2020). Commercial βCD:EPI macroparticles were used for the removal of twenty one different drugs existing in wastewater effluents. The adsorption process is carried out together with a photodegradation treatment. The results show a removal efficiency of 71% after 5 min for most of the drugs, whereas a 99% removal is reached for metoprolol, paroxetine and propranolol. Generally, the removal efficiency follows the order: β‒blockers > psychiatric drugs > lipid regulators > antibiotics > anti‒inflammatories > diuretics (Gómez-Morte et al., 2021). Additionally, fibers of HP-βCD:EPI have been evaluated as adsorbent for removal of phenanthrene—a compound used for the synthesis of bile acids and steroids. It has been found that these fibers were able to remove 80% of phenantrene (Celebioglu et al., 2019).

Nanosponges of αCD, βCD and γCD crosslinked with citric acid have been evaluated by Moulahcene et al. for the sorption of progesterone. The αCD:CA NS showed the best sorption performance in continuous flow column (95%); that was justified by the lower swelling ability, higher surface area and number of acidic groups (among all three NSs). (Moulahcene et al., 2015).

βCD:EDTA was applied for the removal of ciprofloxacin, a quimolone antibiotic, having reached a maximum sorbed amount of 327 mg g⁻¹, at a pH range 4–6. The sorption mechanism is sensitive to the ionic strength, probably due to screening effect caused by the counterions (Yu F. et al., 2018). The ciprofloxacin removal was further studied with αCD, βCD and γCD crosslinked with BDE and the removal efficiency was also quite promising (i.e., 90%). In a similar way, the sorption capacity is impaired by the presence of salts and pH changes (Rizzi et al., 2021).

In an interesting study, βCD nanosponges obtained using aliphatic and aromatic linkers of the diisocyanate class, dicyclohexylmethane-4,4′-diisocyanate (CHI) and MDI, respectively, were compared. Three molar ratios, 1:1, 1:2 and 1:3 mol/mol were used. The polymers present different hydrophilic/hydrophobic ratios. Tests were performed on artificial and human urines to analyse sorption abilities for testosterone, epitestosterone, androsterone, etiocholanolone, 5α‒androstane-3α,17β-diol and 5β-androstane-3α,17β‒diol. βCD:CHI at molar ratio 1:1 showed the best performance for each analyte with accuracy and recovery within 96 and 106%, respectively. The superior performance of βCD:CHI can be justified considering the higher mobility and flexibility of the aliphatic linker, making the active sites more easily accessible (Manaf et al., 2018).

Materials already mentioned in previous sections were also applied for pharmaceutical removal. βCD:TFP has been used for a number of studies involving the adsorption of many drugs. The properties of βCD:TFP are dependent on the solvent and CD:crosslinker molar ratio (Klemes et al., 2018) (Li C. et al., 2018). Among the adsorbates evaluated we can mention ethynyl oestradiol and propranolol hydrochloride (Alsbaiee et al., 2016; Wang Z. et al., 2019), and chloroxylenol and carbamazepine (Zhou Y. et al., 2019). With few exceptions, this NS reached efficiencies higher than 70%, which shows a high affinity of NSs for different kinds of pharmaceutical molecules.

Moreover, four types of nanosponges with different crosslinkers, namely, PMA, CDI, CA and TDI, were synthesised. βCD:PMA and βCD:CA show the higher level of swelling justified by the larger number of donator and acceptor hydrogen bonding. The removal efficiency of the NSs was tested for indole in three different media: water, simulated gastric fluid and intestinal fluid. Indole is produced by tryptophan conversion, and it is a precursor of uremic toxins responsible of several severe health illnesses. The removal ability of the materials for indole decrease in the following order: βCD:TDI (≈91%)>βCD:CA>βCD:PMA>βCD:CDI (Varan et al., 2020).

Biphenols are derivatives of phenol used in the manufacture of plastic furniture and are key components of liquid crystal polymers. Nonetheless, due to their high volume of production and usage, they are classified as persistent organic pollutants. They are hazardous for the environment and for human health. Bisphenol A (BPA) is the most produced and thus the most common in water bodies. Consequently, there is a demand for adsorbents capable of removing these pollutants. The aromatic ring of these compounds can strongly interact, via host-guest interaction, with CD, making CDNSs ideal for that purpose. In fact, several CDNS adsorbents were studied and high removal efficiencies were reported. For example, βCD:EPI, βCD:PFP:CTS/EDTA, βCD:P5 and βCD:TFP:THTS have RE greater than 90% in the removal of Bisphenol A (Alsbaiee et al., 2016; Yu et al., 2018c; Wang Z. et al., 2019; Lu et al., 2019).

Other biphenols with less environmental impact were also tested. Thus, the bisphenol S (BPS) (an endocrine disruptor) has a significant interaction with βCD:FPS (1:2 mol/mol) leading to a removal efficiency ≥80% (Wang et al., 2017). The removal of bisphenol F (BPF) and bisphenol AF (BPAF) was also studied by using βCD:CMP. This NS shows a high sorption efficiency due to its larger surface area and a significant number of π‒π interactions (Huang et al., 2020).

Particularly interesting is a study carried out for assessing the adsorption capacity of heptakis(2,6‒di‒O‒methyl)βCD crosslinked with three different diisocyanates [MDI, 1,4‒phenylene diisocyanate (PDS) and HDI]. Sixty six different biphenyls, from mono to decachlorobiphenyls, using isooctane as solvent, were tested. The highest crosslinked βCD:MDI and βCD:PDS showed adsorption performances around 100%. This behaviour is also dependent on the CD concentration (Kawano et al., 2015).

In a previous section, the ability of CDNSs for the removal of pesticides and other pollutants has been summarized. In this section, we discuss the role of CDs based on a different approach. In order to reduce the amount of pesticides applied in agriculture, the exposure of workers, and to ameliorate the efficiency of the phytopharmaceuticals, a broad range of materials have been developed. Nanosponges of αCD, βCD and γCD were prepared using 1,1′-carbonyldiimidazole (CDI) and PMA as crosslinkers. Both types of nanosponges were loaded in methanol with ailanthone, a natural herbicide characterized by low persistence and rapid degradation. γCD-based materials showed higher interaction for ailanthone with 55% of encapsulation efficiency (EE) and remarkable efficacy on index growth of garden cress and radish after 10 days. The highest EE is found for γCD-based NS, probably due to proper fit between cavity and analyte sizes (Demasi et al., 2021) (Demasi et al., 2021). Additionally, βCD:PMA was synthesized at molar ratio 1:12 mol/mol by electrospinning in fibers with 3 µm diameter. It was applied as micropesticide, loaded with a maximum of 130 mg g⁻¹ of N,N-diethyl-3-toluamide (DEET), a common insecticide, with a release of 60% in 72 h and 100% at about 350 h (Cecone et al., 2018).

Cyclodextrin‒materials can be applied as direct or indirect sensor materials via turn‒on or turn‒off of fluorescence both via host‒guest complexation or molecular assembly with fluorescent/luminescent probe molecules.

Fluorescent cyclodextrin‒based probe was obtained via cross-linking of βCD with 4,4′‒diisocyanato‒3,3′‒dimethyl biphenyl (IMP) and tetrakis (4‒hydroxyphenyl)ethane (TPE) as fluorescent ligands. The fluorescent βCD‒polymer was successfully applied for the detection of trinitrophenol and nitrobenzene by turn‒off. These aromatic compounds are used for dye and pesticide synthesis, presenting hazardous effects for human health and possible environment contamination (Danquah et al., 2019). βCD:PMA was prepared at molar ratio of 1:7 mol/mol as fluorescent probe with emission wavelength at 423 nm. The polymeric material has an heterogeneous size distribution with a high polydispersity index. It presents an excellent selectivity for diclofenac (LOD 0.92 µM) in aqueous solution and tablets, whose value is not significantly influenced by the presence of different drugs, probably due to more hydrophobic behaviour of the diclofenac (Nazerdeylami et al., 2021).

Being CD nanosponges porous polymeric materials, often with a large active surface area and numerous available active sites, they are considered promising materials to be used as heterogeneous catalysts.

βCD:CDI with 11 m² g⁻¹ of active surface and nanoporous structure (5 nm) has promising activity as a metal free catalyst in a one-pot three component condensation reaction (between aromatic aldehydes, methylene compounds and amines) for the synthesis of N-containing organic scaffolds (Sabzi and Kiasat, 2018). βCD:EPI (surface area of 11 m² g⁻¹ and 5 nm of pore diameter) was applied in a four component solvent-free reaction for the synthesis of spiro [indoline‒3,4′‒pyrano(2,3‒c)pyrazole] and pyranopyrazole derivatives. However, the reaction only proceeds with high yield at 100°C (Jafari Nasab et al., 2018). In another paper, a heteropolyacid was immobilized onto βCD:DPC (3 m² g⁻¹ and pore size 14 nm) and applied as catalyst for the synthesis of xanthenes in high yields (87–95%), at reflux, in short reaction times (Sadjadi et al., 2017b). The same authors also described the use of NSs modified with an ionic liquid, that was used in a cascade reaction for the synthesis of benzochromeno-pyrazole derivatives (Sadjadi et al., 2017a). High yields were obtained using solvent-free conditions, at 80°C.

Amino-βCD NSs were covalently bonded to chitosan beads to prepare a thermally stable porous composite, with surface area 11 m² g⁻¹. βCD:CS was applied as metal free catalyst for the synthesis of dihydropyrimidinone and octahydroquinazolinone in water, via the Biginelli reaction. The composite reveals excellent catalyst activity, with yields up to 100%, using an ultrasonic assisted procedure at 25°C. The composite was reused and a yield decrease of approximately 10% was observed, after five cycles (Sadjadi and Koohestani, 2021a).

Heterogeneous catalysts based on CD nanosponges and containing embedded inorganic nanoparticles were also described. However, since the aim of this review is focused on pure CDNSs, these studies will not be reported in detail, just a brief classification based on the type of metal used is given: 1) Pd⁰/Pd²⁺ for hydrogenation reactions (Sadjadi and Koohestani, 2021b), cyanation reactions (Khajeh Dangolani et al., 2019), Sonogashira and Heck (Sadjadi et al., 2018b; 2019b); 2) Ag⁺ for redox reactions (Russo et al., 2019); 3) Au for 4‒nitrophenol synthesis (Vasconcelos et al., 2016).