Cyclodextrin Host Research Articles

Encapsulation of Vecuronium and Rocuronium by Sugammadex Investigated by Surface-Enhanced Raman Spectroscopy.

Aiming toward a novel, noninvasive technique, with a real-time potential application in the monitoring of the complexation of steroidal neuromuscular blocker drugs Vecuronium (Vec) and Rocuronium (Roc) with sugammadex (SDX, medication for the reversal of neuromuscular blockade induced by Vec or Roc in general anesthesia), we developed proof-of-principle methodology based on surface-enhanced Raman spectroscopy (SERS). Silver nanoparticles prepared by the reduction of silver ions with hydroxylamine hydrochloride were used as SERS-active substrates, additionally aggregated with calcium nitrate as needed. The Vec and Roc SERS spectra were obtained within the biorelevant 5 × 10-7-1 × 10-4 M range, as well as the SERS of SDX, though the latter was observed only in the presence of the aggregating agent. SDX/drug complexes at a 1/1 molar ratio revealed significant spectral changes in the vibrational bands of the SDX glucose rings and the drug steroid rings, implying that the insertion of Vec and Roc molecules into the SDX cavity was not only driven by attractive electrostatic interactions between the positively charged cyclic unit of the drug and the negative carboxylate groups of cyclodextrin but also supported by hydrophobic interactions between the host cyclodextrin and the guest drug molecule. The observed changes in SERS signals are applicable in biorelevant conditions and support further studies of SDX/drug complexes in vivo.

Screening Cyclodextrin Complexes for Bisphenols with High Binding Performance Based on the Data-Driven Model.

The distinctive cavity structure of cyclodextrin, which results in binding properties, is credited with its application prospects in chemical, pharmacy, and material fields. The binding capacity can be regulated by substituting the hydroxyl groups on the cyclodextrins. It is possible to acquire anticipated binding properties by designing the modified groups on cyclodextrins. In this article, a data-driven model is proposed with a novel cyclodextrin/guest structure representation method to assist the cyclodextrin design. The model's performance is verified via several validations, as the squared correlation coefficients for cross-validation (Q2) and test set (R2test) are 0.801 and 0.841, respectively. With the proposed model and fluorescence experiments for cyclodextrin/bisphenol complexes, several cyclodextrin hosts, which have a strong binding capacity for bisphenols, are screened, synthesized, and characterized. The results show a controlled average absolute error of 0.605 M-1, suggesting the feasibility of data supplementation and molecular design. It is believed that the data-driven model can serve as theoretical assistance and a driving tool for the cyclodextrin complexes design, potentially leading to advancements in cyclodextrin's industrial applications and scientific research.

β-Cyclodextrin-Modified Cotton Fabric for Medical and Hospital Applications with Photodynamic Antibacterial Activity Using Methylene Blue

The use of cyclodextrins in textiles for the development of biofunctional fabrics represents an interesting alternative for the advancement of dental, medical, and hospital materials. Cyclodextrins can interact with the chemical groups present in cotton fibers, leading to the formation of a nanostructured surface with specific functional properties, including antibacterial activity. Although there are numerous antibacterial textile finishes, the use of methylene blue as a cyclodextrin host molecule for photodynamic applications in textile materials remains to be investigated. This is because methylene blue is a photosensitive dye capable of generating singlet oxygen (1O2) when illuminated, which inactivates the pathogenic microorganisms that may be present in wounds. The objective of this study was to develop a biofunctionalized and photoactivatable cotton fabric with antimicrobial properties for use in the cosmetic or medical industries. The materials obtained were characterized via scanning electron microscopy (SEM), Fourier transform infrared spectroscopy with attenuated total reflection (FTIR-ATR), the determination of cotton fabric functionalization dyeing variables, colorimetry, UV-VIS spectrophotometry, degradation of 9,10-anthracenediyl-bis(methylene)dimalonic acid (ABDA), photodegradation tests, and microbiological analysis. The results showed that the textile was functionalized with β-cyclodextrin, mainly evidenced by the appearance of the band at 1730 cm−1, indicating the formation of the ester group. Thus, when exposed to light, the non-functionalized material showed greater photobleaching, about 60%, compared to the material treated with cyclodextrin. This result was also reflected in the ABDA degradation kinetics, with the treated material showing 592.00% (first phase) and 966.20% (second phase) higher degradation than the untreated sample. Finally, the photodynamic activity was determined based on the antimicrobial properties of the textile, showing a reduction of more than 99% without exposure to light and 100% when exposed to light. It is believed that this study could open avenues for future research and the development of antimicrobial fabrics, as well as demonstrate the efficiency of the treatment with cyclodextrin in relation to photobleaching.

In silico and in vitro study of pyrimidones synthesized with ethylenediamine- modified β-cyclodextrin: potential against ESBL E. coli

Modern organic synthesis is primarily focused on developing environmentally benign synthetic protocols by employing green chemistry principles. Accordingly, in our recent research work, we herein report the use of modified supramolecular host cyclodextrin as an effective solid based green catalyst for accessing structurally diverse and medicinally relevant pyrimidone architectures. The catalyst and the synthesized compounds 4 (a-r) were characterized using FT-IR, NMR and GC-mass spectroscopy. Major highlights of the reported work include the economical atom process, remarkably gentler reaction conditions, ease of operation, high isolated yields, and excellent catalyst turnover numbers. The molecular docking studies suggest that the compound 4n has hydrogen bonding, hydrophobic and π-pair interactions with the active site of the CXT M 15 receptor. Further, the in-vitro antibacterial study as well as the screening of anti-biofilm activity resulted in a BIC value of 76.79 ± 0.785% at a concentration of 10 µg/mL and morphological alterations induced by DHPMs against the ESBL E. coli strain aggregated with a good result. KEY WORDS: Ethylenediamine modified β-CD, Multicomponent reaction, 3,4-dihydropyrimidin-2(1H)-ones DHPM derivatives, Solvent-free conditions, Reusability, Antibactercidal Bull. Chem. Soc. Ethiop. 2024, 38(4), 1103-1118. DOI: https://dx.doi.org/10.4314/bcse.v38i4.23

Gas-phase solvent-free complexation of phenolic acids in cyclodextrins: A mass spectrometric study

Phenolic acids are phytochemicals commonly existing in plants that are also beneficial to the human body after consumption. As additives in the food industry, phenolic acids typically need stabilization by encapsulation. We have been studying cyclodextrins as potential encapsulating agents, elucidating the structure and energetics of the complexes they form with phenolic acids. To highlight the role of the solvent in these interactions and to investigate the possible component ratios available to these complexes, we first carried out gas-phase studies monitored through mass spectrometry that allowed us to work in solvent-free conditions. In addition to detecting the products of these complexation equilibria qualitatively, we were also able to find conditions to quantitative determine the relative binding affinities associated with these processes. As well as on the unusual complex stoichiometry observed in the gas phase for a series of phenolic acids with α-CD, β-CD, and γ-CD. We propose an explanation of these uncommon stoichiometries through solvation effects involving the cyclodextrin host as the solvating species. We also report on the observed trends in the measured relative affinities of these interactions.

Spatial arrangements of cyclodextrin host-guest complexes in solution studied by 13C NMR and molecular modelling.

13C NMR spectroscopic analyses of Cs symmetric guest molecules in the cyclodextrin host cavity, combined with molecular modelling and solid-state X-ray analysis, provides a detailed description of the spatial arrangement of cyclodextrin host-guest complexes in solution. The chiral cavity of the cyclodextrin molecule creates an anisotropic environment for the guest molecule resulting in a splitting of its prochiral carbon signals in 13C NMR spectra. This signal split can be correlated to the distance of the guest atoms from the wall of the host cavity and to the spatial separation of binding sites preferred by pairs of prochiral carbon atoms. These measurements complement traditional solid-state analyses, which rely on the crystallization of host-guest complexes and their crystallographic analysis.

The SAMPL9 host-guest blind challenge: an overview of binding free energy predictive accuracy.

We report the results of the SAMPL9 host-guest blind challenge for predicting binding free energies. The challenge focused on macrocycles from pillar[n]-arene and cyclodextrin host families, including WP6, and bCD and HbCD. A variety of methods were used by participants to submit binding free energy predictions. A machine learning approach based on molecular descriptors achieved the highest accuracy (RMSE of 2.04 kcal mol-1) among the ranked methods in the WP6 dataset. Interestingly, predictions for WP6 obtained via docking tended to outperform all methods (RMSE of 1.70 kcal mol-1), most of which are MD based and computationally more expensive. In general, methods applying force fields achieved better correlation with experiments for WP6 opposed to the machine learning and docking models. In the cyclodextrin-phenothiazine challenge, the ATM approach emerged as the top performing method with RMSE less than 1.86 kcal mol-1. Correlation metrics of ranked methods in this dataset were relatively poor compared to WP6. We also highlight several lessons learned to guide future work and help improve studies on the systems discussed. For example, WP6 may be present in other microstates other than its -12 state in the presence of certain guests. Machine learning approaches can be used to fine tune or help train force fields for certain chemistry (i.e. WP6-G4). Certain phenothiazines occupy distinct primary and secondary orientations, some of which were considered individually for accurate binding free energies. The accuracy of predictions from certain methods while starting from a single binding pose/orientation demonstrates the sensitivity of calculated binding free energies to the orientation, and in some cases the likely dominant orientation for the system. Computational and experimental results suggest that guest phenothiazine core traverses both the secondary and primary faces of the cyclodextrin hosts, a bulky cationic side chain will primarily occupy the primary face, and the phenothiazine core substituent resides at the larger secondary face.

Deciphering the mechanism of γ-cyclodextrin's hydrophobic cavity hydration: an integrated experimental and theoretical study.

Cyclodextrins (CDs) are host systems with inherent capability for inclusion complex formation with various molecular entities, mostly hydrophobic substances. Host CDs are highly accommodative to water molecules as well and usually contain water in the native state. There is still an ongoing discussion on both the total number of water molecules and their preferred binding position inside the cavities of the CDs. To understand the hydration/dehydration properties of γ-CD (the largest of the three most abundant native CDs), the main experimental methods applied in this study were differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). By coupling these techniques with density functional theory (DFT) calculations we try to shed some light on the mechanism of the γ-CD hydration and to address some unanswered questions: (i) what are the preferable locations for water molecules in the macrocyclic cavity ("hot spots"); (ii) what are the major factors contributing to the stability of the water cluster in the CD interior; (iii) what type of interactions (i.e., water-water and/or water-CD walls) contribute to the stability of the water assemble; (iv) how does the mechanism of the γ-CD hydration compare with those of its α-CD and β-CD counterparts.

Hybridizing a Dual-Cross Network and a Linear Glassy Polymer for Dynamic Contributions to High Mechanical Toughness Based on Phase-Separated Structures

Bulk copolymerization of alkyl acrylate and cyclodextrin (CD) host monomers forms a single movable cross network (SC), in which the CD units act as movable cross-linkers. Moreover, the bulk copolymerization of the CD monomer and main chain monomer in the presence of SC results in dual-cross-network (DC) elastomers. DC elastomers result in good toughness (Gf). Here, to improve Gf and Young’s modulus (E), we hybridized DC elastomers with tertiary glassy polymers, which are called DCP elastomers. We prepared the DCP elastomers by photopolymerization of N,N-dimethylacrylamide (DMAA) and poly(2-methoxyethyl acrylate) (MEA) in the presence of DC. A DCP elastomer with a suitable weight percent (wt %) of the glassy polymer shows high Gf (108.4 MJ m–3) and E (223.4 MPa) values. Dynamic mechanical analysis (DMA) and in situ small-angle X-ray scattering (SAXS) measurements under uniaxial stretching indicate multiple deformations based on phase-separated structures. We suggest that the phase-separated structures of DCP elastomers cause a large stress dissipation, which contributes to high toughness.

Preparation, physicochemical characterization and computational studies of Plectranthus ornatus codd essential oil/β-cyclodextrin inclusion complex

This study aims to prepare and chemically characterize inclusion complexes (IC) between β-cyclodextrin (β-CD) and Plectranthus ornatus essential oil (OEPO). Samples were evaluated by gas chromatography coupled with mass spectrometry (GC-MS) and Fourier transform infrared spectroscopy (FTIR). Moreover, a theoretical study concerning inclusion complexes of β-CD with the four main compounds of OEPO through Molecular Dynamics (MD) simulations, Density Functional Theory (DFT) and Parametric Method-6 (PM6) calculations was performed. The GC-MS analysis of OEPO resulted in the identification of 36 volatile compounds, with the four main components of this essential oil being: β-caryophyllene (21.52%), terpinen-4-ol (6.89%), phytol (4.00%) and caryophyllene oxide (3.32%). The GC-MS results indicated the presence of OEPO volatile compounds in the ICs prepared by the water/ethanol kneading (KWE) and water kneading (KW) method. More specific, β-CD inclusion complexes with β-butoxyethanol (1.15%), 1,3,8-ρ-menthatriene (0.45%), β-caryophyllene (0.20%), phytol (0.41%) and δ-cadinol (0.20%) prepared by the KWE method were detected, while the KW inclusion method resulted in the encapsulation of β-butoxyethanol (3.98%) only. The higher inclusion content of OEPO molecules in KWE was also confirmed by FTIR, with the KWE complex showing more OEPO absorption bands than KW. The PM6 study showed that hydrogen bonds are important, but hydrophobic interactions are the main driving force for triggering the complex formation of the main OEPO volatile compounds with β-CD. The intermolecular host-guest interactions and the investigation for the most suitable inclusion mode were examined by conducting several Molecular dynamics simulations. Moreover, PM6 and DFT approaches revealed the most stable cyclodextrin inclusion complex structures. These findings are in accordance with the experimental data from GC-MS analysis. The effect of solvent on the interaction energy was also studied through simulations and the results showed that the most stable structures are characterized by the formation of hydrogen bonds between guests and cyclodextrin hosts. The developing of such preparation methods that results in ICs like OEPO/β-CD may be useful in the optimization of existing formulations and therefore, be adopted by the pharmaceutical industry

Taming multiple binding poses in alchemical binding free energy prediction: the β-cyclodextrin host-guest SAMPL9 blinded challenge.

We apply the Alchemical Transfer Method (ATM) and a bespoke fixed partial charge force field to the SAMPL9 bCD host-guest binding free energy prediction challenge that comprises a combination of complexes formed between five phenothiazine guests and two cyclodextrin hosts. Multiple chemical forms, competing binding poses, and computational modeling challenges pose significant obstacles to obtaining reliable computational predictions for these systems. The phenothiazine guests exist in solution as racemic mixtures of enantiomers related by nitrogen inversions that bind the hosts in various binding poses, each requiring an individual free energy analysis. Due to the large size of the guests and the conformational reorganization of the hosts, which prevent a direct absolute binding free energy route, binding free energies are obtained by a series of absolute and relative binding alchemical steps for each chemical species in each binding pose. Metadynamics-accelerated conformational sampling was found to be necessary to address the poor convergence of some numerical estimates affected by conformational trapping. Despite these challenges, our blinded predictions quantitatively reproduced the experimental affinities for the β-cyclodextrin host and, to a lesser extent, those with a methylated derivative. The work illustrates the challenges of obtaining reliable free energy data in in silico drug design for even seemingly simple systems and introduces some of the technologies available to tackle them.

Multiple Effects of an Anionic Cyclodextrin Macrocycle on the Reversible Isomerization of a Photoactive Guest Dye.

Understanding and controlling the reversible isomerization of photoactive molecules in order to obtain a tunable optical response is desirable for many photofunctional applications. This study describes the interesting effects of an anionic cyclodextrin host (sulfated-βCD, SCD) on the photoisomerization and protonation equilibrium of an important hemicyanine dye (trans-4-[4-(dimethylamino)styryl]-1-methylpyridinium iodide, DSP). The SCD host assists in unlocking the photoisomerization potential of DSP by promoting protonation of the dye. It also assists in stabilizing the cis isomer of the protonated dye, thereby significantly delaying the reverse cis to trans isomerization of DSPH+. Furthermore, the interplay of both hydrophobic and electrostatic interactions in the complex formation of SCD with DSPH+ makes the reverse cis to trans isomerization of DSPH+ amenable to influence by the added salt. The stimuli-responsive reversible isomerization of SCD-DSPH+ is an interesting case from the perspective of chemical sensing or light operated functional materials with host-guest systems.

Multi-equilibrium approach to study cyclodextrins host–guest systems with GFN2-xTB quantum method: A case study of phosphorothioates included in β-cyclodextrin

Computing equilibrium constants for cyclodextrin host–guest systems is challenging and prohibitive, depending on the quantum method chosen. We propose applying a multi-equilibrium approach to estimate stability constants for Cyclodextrin (CD) systems with the robust semiempirical GFN2-xTB method and using the User-Defined Association Parameters (UD-APARM) software. The host–guest systems formed with β-CD and some phosphorothioates were studied in the present work due to their structural diversity and reported experimental data. As a result, we obtained an excellent linear correlation with the experiment for systems formed by β-CD and diazinon (DZN), parathion (PTN), methyl parathion (MPTN), and chlorpyrifos (CPF). The obtained linear correlation was then applied to estimate the stability constants for the inclusion of chlorethoxyfos (CEF) and tebupirimfos (TPF) in β-CD, for which no experimental data is known. We discuss the applicability of the workflow adopted for sampling CD-based host–guest supramolecular space with UD-APARM and semiempirical GFN2-xTB method.

Sugammadex analogue cyclodextrins as chiral selectors for enantioseparation of cathinone derivatives by capillary electrophoresis

The present contribution describes the application of three single-isomeric cyclodextrin derivatives for the first time – Sugammadex, Subetadex and Sualphadex as chiral selectors. Their recognition ability was investigated by means of chiral capillary electrophoresis, on a pool of cathinone and amphetamine derivatives. The selectors differ in cavity sizes and in the number of ionizable groups which evidently influenced their enantioselectivity performance. Their common feature is their high isomeric purity that enabled the detailed study of the molecular association between the cathinone guest and the cyclodextrin host at the atomic level. With the aid of enantiopure cathinone derivatives, the migration order could also be determined in capillary electrophoresis. As the result of the capillary electrophoresis screening, partial or baseline chiral separation of 19 cathinones and an amphetamine derivative could be achieved, and the systematic study was performed focusing on three different pH conditions pH = 7.0, pH = 5.0 and pH = 2.5 and several different selector concentrations. Among the tested derivatives Subetadex is the best performing chiral selector, especially under acidic pH values for separating enantiomers, proven not only by capillary electrophoresis but also by 1D and 2D NMR measurements.

Current Status of Quantum Chemical Studies of Cyclodextrin Host-Guest Complexes.

This article aims to review the application of various quantum chemical methods (semi-empirical, density functional theory (DFT), second order Møller–Plesset perturbation theory (MP2)) in the studies of cyclodextrin host–guest complexes. The details of applied approaches such as functionals, basis sets, dispersion corrections or solvent treatment methods are analyzed, pointing to the best possible options for such theoretical studies. Apart from reviewing the ways that the computations are usually performed, the reasons for such studies are presented and discussed. The successful applications of theoretical calculations are not limited to the determination of stable conformations but also include the prediction of thermodynamic properties as well as UV–Vis, IR, and NMR spectra. It has been shown that quantum chemical calculations, when applied to the studies of CD complexes, can provide results unobtainable by any other methods, both experimental and computational.

Host-guest interactions based supramolecular complexes self-assemblies for amplified chemodynamic therapy with H2O2 elevation and GSH consumption properties

Although endogenous H2O2 is overexpressed in tumor tissue, the amount of endogenous H2O2 is still insufficient for chemodynamic therapy (CDT). In addition, the abundant cellular glutathione (GSH) could also consume •OH for reduced CDT. Thus, the elevation of H2O2 and the consumption of GSH in tumor tissue are essential for the increased •OH yield and amplified CDT efficacy. In this paper, host-guest interactions based supramolecular complexes self-assemblies (SCSAs) were fabricated by incorporating cinnamaldehyde (CA) and PEG-modified cyclodextrin host units (mPEG-CD-CA) with ferrocene-(phenylboronic acid pinacol ester) conjugates (Fc-BE) on the basis of CD-induced host-guest interactions. After being internalized by cancer cells, CA can be released from SCSAs through the pH-responsive acetal linkage, elevating the H2O2 level by activating NADPH oxidase. Then, Fc can catalyze the H2O2 to higher cytotoxic hydroxyl radicals (•OH). Moreover, quinone methide (QM) can be produced through H2O2-induced aryl boronic ester rearrangement and further consume the antioxidant GSH. In vitro and in vivo experiments demonstrate that SCSAs can be provided as potential amplified CDT nanoagents.

Preparation of dual-cross network polymers by the knitting method and evaluation of their mechanical properties

Bulk copolymerization of alkyl acrylates and cyclodextrin (CD) host monomers produced a single movable cross-network (SC). The CD units acted as movable crosslinking points in the obtained SC elastomer. Introducing movable crosslinks into a poly(ethyl acrylate/butyl acrylate) copolymer resulted in good toughness (Gf) and stress dispersion. Here, to improve the Young’s modulus (E) and Gf of movable cross-network elastomers, the bulk copolymerization of liquid alkyl acrylate monomer swelling in SC gave another type of movable cross-network elastomer with penetrating polymers (SCPs). Moreover, the bulk copolymerization of alkyl acrylate and the CD monomer in the presence of SC resulted in dual cross-network (DC) elastomers. The Gf of the DC elastomer with a suitable weight % (wt%) of the secondary movable cross-network polymer was higher than those of the SCP or SC elastomers. The combination of suitable hydrophobicity and glass transition of the secondary network was important for improving Gf. Small-angle X-ray scattering (SAXS) indicated that the DC elastomers exhibited heterogeneity at the nanoscale. The DC elastomers showed a significantly broader relaxation time distribution than the SC and SCP elastomers. Thus, the nanoscale heterogeneity and broader relaxation time distribution were important to increase Gf. This method to fabricate SCP and DC elastomers with penetrating polymers would be applicable to improve the Gf of conventional polymeric materials.

Hydrogel Transformed from Nanoparticles for Prevention of Tissue Injury and Treatment of Inflammatory Diseases

Functional hydrogels responsive to physiological and pathological signals have extensive biomedical applications owing to their multiple advanced attributes. Herein, engineering of functional hydrogels is reported via transformable nanoparticles in response to the physiologically and pathologically acidic microenvironment. These nanoparticles are assembled by a multivalent hydrophobic, pH-responsive cyclodextrin host material and a multivalent hydrophilic guest macromolecule. Driven by protons, the pH-responsive host-guest nanoparticles can be transformed into hydrogel, resulting from proton-triggered hydrolysis of the host material, generation of a hydrophilic multivalent host compound, and simultaneously enhanced inclusion interactions between host and guest molecules. By in situ forming a hydrogel barrier, the orally delivered transformable nanoparticles protect mice from ethanol- or drug-induced gastric injury. In addition, this type of nanoparticles can serve as responsive and transformable nanovehicles for therapeutic agents to achieve triggerable and sustained drug delivery, thereby effectively treating typical inflammatory diseases, including periodontitis and arthritis in rats. With combined advantages of nanoparticles and hydrogels, together with their good in vivo safety, the engineered transformable nanoparticles hold great promise in tissue injury protection and site-specific/local delivery of molecular and cellular therapeutic agents.

Dynamic nanosurface reconfiguration by host-guest supramolecular interactions.

The dynamic functionalization of the nanoparticle surface with biocompatible coatings is a critical step towards the development of functional nano-sized systems. While covalent approaches have been broadly exploited in the stabilization of nanoparticle colloidal systems, these strategies hinder the dynamic nanosurface chemical reconfiguration. Supramolecular strategies based on specific host-guest interactions hold promise due to their intrinsic reversibility, self-healing capabilities and modularity. Host/guest couples have recently been implemented in nanoparticle platforms for the exchange and release of effector molecules. However, the direct exchange of biocompatible hydrophilic oligomers (e.g. peptides) for the modulation of the surface charge and chemical properties of nanoparticles still remains a challenge. Here, we show the intracellular reconfiguration of nanoparticles by a host/guest mechanism with biocompatible oligomeric competitors. The surface of gold nanoparticles was functionalized with cyclodextrin hosts and the guest exchange was studied with biocompatible mono and divalent adamantyl competitors. The systematic characterization of the size and surface potential of the host/guest nanoparticles allowed the optimization of the binding and the stabilization properties of these supramolecular systems. The in cellulo host/guest-mediated direct reconfiguration of the peptide layer at the surface of nanoparticles is achieved by controlling the valence of adamantane-equipped peptides. This work demonstrates that host/guest supramolecular systems can be exploited for the direct exchange of pendants at the surface of nanoparticles and the intracellular dynamic chemical reconfiguration of biocompatible colloidal systems.

Photo-Responsive Self-Assembly of Plasmonic Magnetic Janus Nanoparticles.

Stimuli-responsive self-assembly of nanoparticles is a versatile approach for the bottom-up fabrication of adaptive and functional nanomaterials. For this purpose, anisotropic building blocks are of particular importance due to the unique shapes and structures that can be obtained upon self-assembly. Here, we demonstrate the photo-responsive self-assembly of plasmonic magnetic "dumbbell" Janus nanoparticles (Au-Fe3O4) via the host-guest interaction of the supramolecular host cyclodextrin and the molecular photoswitch arylazopyrazole. We developed efficient ligand exchange procedures that enable the introduction of functional ligands, respectively, to the surface of the gold or magnetite core of the dumbbell. Our results indicate that distinct nanoparticle superstructures arise in aqueous solutions if nanoparticle aggregation is crosslinker-induced or self-induced and that the reversible formation and fragmentation of the superstructures can be modulated with light.