Cytotoxicity Regulated by Host–Guest Interactions: A Supramolecular Strategy to Realize Controlled Disguise and Exposure

This work is aimed at providing a supramolecular strategy for tuning the cytotoxicity in chemotherapy. To this end, as a proof of concept, we employed dynamic cucurbit[7]­uril­(CB[7])-mediated host–guest interaction to control the loading and releasing of dimethyl viologen (MV) as a model antitumor agent. MV has high cytotoxicity to both normal cells and tumor cells without specificity. By encapsulating MV into the hydrophobic cavity of CB[7], the cytotoxicity of MV to normal cells can be significantly decreased. When the host–guest complex of MV-CB[7] is added into tumor cells with overexpressed spermine, the antitumor activity of MV can be recovered in tumor cell environment. There are two reasons behind this effect: on the one hand, spermine has a high affinity to CB[7], leading to releasing of MV from MV-CB[7]; on the other hand, CB[7] can soak up spermine, which is essential for tumor cell growth, therefore decreasing the cell viability furthermore. Then, it is highly anticipated that this kind of supramolecular strategy could apply to clinical antitumor agents and provide a new approach for decreasing the cytotoxicity and increasing the antitumor activity, thus opening horizons of supramolecular chemotherapy

Supramolecular Interfacial Polymerization of Miscible Monomers: Fabricating Supramolecular Polymers with Tailor-Made Structures

We have fabricated a series of supramolecular polymers with tailor-made structures and properties through supramolecular interfacial polymerization of miscible monomers. Compared with homogeneous solution polymerization, supramolecular interfacial polymerization is advantageous for fabricating supramolecular polymers with higher molecular weights. Their higher molecular weights are attributed to the higher effective concentration of monomers at the interface than in solutions and diffusion-limited characteristic of supramolecular interfacial polymerization. Moreover, the glass transition temperatures of supramolecular polymers are well tuned by tuning the monomer structures and supramolecular interfacial copolymerization. It is anticipated that this research will further enrich the methodology for fabricating supramolecular polymers with controlled structures and properties through supramolecular interfacial polymerization

pH-Induced Charge-Reversal Amphiphile with Cancer Cell-Selective Membrane-Disrupting Activity

A charge-reversal amphiphile exhibiting charge conversion from negative to positive induced by pH is reported. It selectively kills cancer cells through cell membrane disruption. This amphiphile comprising an alkyl chain and anionic headgroup of acid-labile β-carboxylic amide (C16N-DCA) was prepared. In the microenvironment of normal cells with pH 7.4, the negatively charged C16N-DCA exhibited considerably reduced cytotoxicity. However, in the acidic microenvironment of cancer cells with pH 6.5–6.8, the headgroup charge of C16N-DCA changed from negative to positive under hydrolysis of the acid-labile amide group. As a result, the generated cationic amphiphile displayed significant killing of cancer cells by disrupting their cell membranes. Such pH-selective cell killing bioactivity represents a new route of chemotherapy for anticancer strategies

Supramolecular Chemotherapy: Cooperative Enhancement of Antitumor Activity by Combining Controlled Release of Oxaliplatin and Consuming of Spermine by Cucurbit[7]uril

Supramolecular chemotherapy is aimed to employ supramolecular approach for regulating the cytotoxicity and improving the efficiency of antitumor drugs. In this paper, we demonstrated a new example of supramolecular chemotherapy by utilizing the clinical antitumor drug, oxaliplatin, which is the specific drug for colorectal cancer treatment. Cytotoxicity of oxaliplatin to the colorectal normal cell could be significantly decreased by host–guest complexation between oxaliplatin and cucurbit[7]­uril (CB[7]). More importantly, oxaliplatin-CB[7] exhibited cooperatively enhanced antitumor activity than oxaliplatin itself. On the one hand, the antitumor activity of oxaliplatin can reappear by competitive replacement of spermine from oxaliplatin-CB[7]; on the other hand, CB[7] can consume the overexpressed spermine in tumor environments, which is essential for tumor cell growth. These two events can lead to the cooperatively enhanced antitumor performance. Supramolecular chemotherapy can be applied to treat with spermine-overexpressed tumors. It is highly anticipated that this strategy may be employed in many other clinical antitumor drugs, which opens a new horizon of supramolecular chemotherapy for potential applications in clinical antitumor treatments

Polypseudorotaxane Constructed from Cationic Polymer with Cucurbit[7]uril for Controlled Antibacterial Activity

This letter is aimed to develop a general strategy to fabricate polypseudorotaxanes with controlled antibacterial activity based on cationic polymers. As a proof of concept, the commercially available antibacterial cationic polymer, ε-poly-l-lysine hydrochloride, was chosen for the demonstration. Using host–guest chemistry, cucurbit[7]­uril (CB[7]), a water-soluble macrocyclic host, was employed to bind with the positive charge and hydrophobic component on ε-poly-l-lysine hydrochlorides for antibacterial regulation. In this way, by tuning the ratio of CB[7] to the cationic polymer, the antibacterial polypseudorotaxane can be obtained, and the antibacterial efficiency can be well tuned from 5% to 100%. This line of research will enrich the field of cationic polymers and polypseudorotaxanes with important functions on precise control over antibacterial activity

Controllable Supramolecular Polymerization Promoted by Host-Enhanced Photodimerization

In this letter, we report a new method of controllable supramolecular polymerization, taking advantage of host-enhanced photodimerization. The low-molecular-weight supramolecular oligomers were formed by noncovalent complexation between cucurbit[8]­urils (CB[8]) and the bifunctional monomers (DBN) with Brooker’s merocyanine moiety (MOED) on either end. Interestingly, when irradiated with UV light, the supramolecular oligomers could transform into supramolecular polymers with high molecular weight. The molecular weight of supramolecular polymers could be controlled by varying the irradiation time. It is highly anticipated that this work can enrich the methods on the modulation of supramolecular polymerization

Supramolecular Chemotherapy: Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Oxaliplatin to Normal Cells and Improving Its Anticancer Bioactivity Against Colorectal Cancer

We have successfully demonstrated that the host–guest complex of carboxylated pillar[6]­arene with oxaliplatin (OxPt) exhibits low cytotoxicity toward normal cells and displays higher anticancer bioactivity against colorectal cancer cells than OxPt itself. Owing to higher binding affinity of carboxylated pillar[6]­arene with spermine (SPM) than that with OxPt, the encapsulated OxPt can be thoroughly released from its host–guest complex by the competitive replacement with SPM. This supramolecular chemotherapy works well both in vitro and in vivo for SPM-overexpressed cancers, such as colorectal cancer. Compared to OxPt itself, the anticancer bioactivity of this host–guest complex is further improved by about 20%. Such an improvement results from the combined effect of controlled release of OxPt from its host–guest complex and simultaneous consumption of SPM by carboxylated pillar[6]­arene. It is anticipated that this supramolecular strategy may be extended to other clinical anticancer drugs for decreasing their severe side effects and improving their anticancer bioactivity, thus enriching the realm of supramolecular chemotherapy

Supramolecular Chemistry of Cucurbiturils: Tuning Cooperativity with Multiple Noncovalent Interactions from Positive to Negative

Rational control of the cooperativity of multiple noncovalent interactions often plays an important role in the design and construction of supramolecular self-assemblies and materials, especially in precision supramolecular engineering. However, it still remains a challenge to control the cooperativity of multiple noncovalent interactions through tuning the hydrophobic effect. In this work, we demonstrate that the binding cooperativity of cucurbit[8]­uril­(CB[8])-mediated homoternary complexes is strongly influenced by the amphiphilicity of guest molecule side groups on account of an interplay between both classical (entropy-driven) and nonclassical (enthalpy-driven) hydrophobic effects. To this end, we rationally designed and prepared a series of guest molecules bearing a benzyl group as the CB[8] homoternary binding motif with various hydrophilic and hydrophobic side groups for cooperative control. By gradually tuning side groups of the guest molecules from hydrophilic to hydrophobic, we are able to control the binding from positive to negative cooperativity. An advanced molecular recognition process and self-assembling system can be developed by adjusting the positive and negative cooperativity. The ability to regulate and control the binding cooperativity will enrich the field of supramolecular chemistry, and employing cooperativity-controlled multiple noncovalent interactions in precision supramolecular engineering is highly anticipated