Chemotherapy is currently one of the most effective ways to treat cancer. However, traditional chemotherapy faces several obstacles to clinical trials, such as poor solubility/stability, non-targeting capability and uncontrollable release of the drugs, greatly limiting their anticancer efficacy and causing severe side effects towards normal tissues. Supramolecular chemotherapy integrating non-covalent interactions and traditional chemotherapy is a highly promising candidate in this regard and can be appropriately used for targeted drug delivery. By taking advantage of supramolecular chemistry, some limitations impeding traditional chemotherapy for clinical applications can be solved effectively. Therefore, we present here a review summarizing the progress of supramolecular chemotherapy in cancer treatment based on host–guest recognition and provide guidance on the design of new targeting supramolecular chemotherapy combining diagnostic and therapeutic functions. Based on a large number of state-of-the-art studies, our review will advance supramolecular chemotherapy on the basis of host–guest recognition and promote translational clinical applications.

The first [2]calix[1]biphenyl-type hybrid[3]arene was synthesized. Its molecular recognition was investigated by using 1-dihexylammonium hexafluorophosphate as a guest.

A gas and photo dual-responsive host–guest recognition motif was established based on a water-soluble pillar[6]arene and an azobenzene derivative in an aqueous medium. This smart inclusion complex was further applied for the construction of a supra-amphiphile, which could reversibly self-assemble into vesicles upon UV/vis irradiation or bubbling with N2/CO2.

A photo-responsive host–guest molecular recognition between a tetracation cyclophane cyclobis(paraquat-p-phenylene) host and an azobenzene-containing guest was constructed. Based on this novel recognition, a supra-amphiphile was constructed and the photo-responsive self-assembly behaviors were investigated.

A host–guest inclusion complex based on a monofunctionalized pillar[5]arene and a tetraphenylethene derivative was prepared, resulting in an enhanced emission from the tetraphenylethene-based guest, which was applied in cell imaging.

A novel AIE-active boron difluoride fluorescent probe P3T was designed and synthesized. P3T exhibited high sensitivity to intra- and extra-cellular pH changes. Furthermore, a Förster resonance energy transfer (FRET) system was constructed, where P3T acted as a donor fluorophore and DOX as the acceptor.

The first cationic water-soluble biphen[3]arene was synthesized and its host–guest complexation with sodium 1-hexanesulfonate was investigated, which was further used to change the aggregation of the amphiphilic guest in water.

A triple-component supra-amphiphile WSP5⊃G1@A is constructed based on phenylboronic acid/diols dynamic covalent chemistry and water-soluble pillararenes/trimethylamine host–guest recognition. Diols-responsive self-assembly of this ternary supra-amphiphile is fully investigated in aqueous solution.

A water-soluble hybrid[4]arene was synthesized for the first time and its pH-responsive host–guest complexation with paraquat in water was investigated. This new host–guest recognition motif was further applied in the construction of a supra-amphiphile.

A dual-responsive supra-amphiphile was successfully constructed between a water-soluble pillar[7]arene and a pyrene-containing guest. The morphologies of the self-assembled materials formed from this supra-amphiphile could be adjusted by changing solution pH or UV irradiation.

A dual-responsive supra-amphiphile was firstly constructed based on a water-soluble pillar[7]arene and a naphthalene diimide-containing guest with a long alkyl chain and a trimethylammonium group. The morphologies of the self-assembly formed from this supra-amphiphile could be adjusted by changing solution pH or adding α-cyclodextrin.

The host–guest complexations between a water-soluble pillar[5]arenes (WP5) and choline derivatives with different alkyl chain lengths were investigated. The hydrophobic interactions played a significant role in these pillar[5]arene-based host–guest complexations. By taking advantage of hydrophobic interactions, the cavity of WP5 could be further employed to inhibit the hydrolysis of acetylcholine in the presence of acetylcholinesterase.

Host–guest complexation between a novel difunctional pillar[5]arene-based host H and alkyldiamines was fully investigated in both solution and the solid state. Proton transfer from the carboxylic acid groups to the amine units occurred in the principle by undergoing an acid–base reaction. Driven by the cooperativity of electrostatic interactions, multiple C–H···π interactions, and H-bonds, the guests penetrated into the cavity of H to form pseudorotaxane-type inclusion complexes with relatively high binding affinities.

A linear supramolecular polymer has been constructed from self-assembly of two complementary homoditopic monomers, an azobenzene-bridged pillar[5]arene dimer and a bisammonium salt, at high concentration based on the pillar[5]arene/secondary ammonium salt molecular recognition motif. This supramolecular polymer exhibited photo and pH dual-responsiveness. Polymer–oligomer and polymer–monomer transitions were reversibly regulated by UV/vis light irradiation and changing the solution pH, respectively. Furthermore, a photo-responsive supramolecular crosslinked liquid-crystalline polymer network based on the host–guest interactions between the azobenzene-bridged pillar[5]arene dimer and a secondary ammonium salt-functionalized poly(methyl acrylate) was fabricated.

A novel molecular recognition motif between a water-soluble pillar[5]arene (WP5) and acetylcholine is established with an association constant of (5.05 ± 0.13) × 104 M−1. Based on this molecular recognition motif, an enzyme-responsive supra-amphiphile is constructed by introducing an amphiphilic guest (PyCh) that is sensitive to acetylcholinesterase. Furthermore, supramolecular hybrid materials are prepared by introducing gold nanoparticles (AuNPs) into these supramolecular systems, which show enzyme-responsive catalytic abilities for the borohydride reduction of 4-nitroaniline.

Proton transfer from a difunctional pillar[5]arene containing two carboxylic acid moieties to amine-based guests occurs in the host–guest complexation. The binding affinities are enhanced effectively due to the existence of electrostatic interactions.

A photo-responsive host–guest molecular recognition between a tetracation cyclophane cyclobis(paraquat-p-phenylene) host and an azobenzene-containing guest was constructed. Based on this novel recognition, a supra-amphiphile was constructed and the photo-responsive self-assembly behaviors were investigated.

A gas and photo dual-responsive host–guest recognition motif was established based on a water-soluble pillar[6]arene and an azobenzene derivative in an aqueous medium. This smart inclusion complex was further applied for the construction of a supra-amphiphile, which could reversibly self-assemble into vesicles upon UV/vis irradiation or bubbling with N2/CO2.

The first [2]calix[1]biphenyl-type hybrid[3]arene was synthesized. Its molecular recognition was investigated by using 1-dihexylammonium hexafluorophosphate as a guest.

A novel AIE-active boron difluoride fluorescent probe P3T was designed and synthesized. P3T exhibited high sensitivity to intra- and extra-cellular pH changes. Furthermore, a Förster resonance energy transfer (FRET) system was constructed, where P3T acted as a donor fluorophore and DOX as the acceptor.

A host–guest inclusion complex based on a monofunctionalized pillar[5]arene and a tetraphenylethene derivative was prepared, resulting in an enhanced emission from the tetraphenylethene-based guest, which was applied in cell imaging.

A dual-responsive supra-amphiphile was firstly constructed based on a water-soluble pillar[7]arene and a naphthalene diimide-containing guest with a long alkyl chain and a trimethylammonium group. The morphologies of the self-assembly formed from this supra-amphiphile could be adjusted by changing solution pH or adding α-cyclodextrin.