Cyclodextrin Molecules Research Articles

Recent Advances in Cyclodextrin-Based Nanoscale Drug Delivery Systems.

Cyclodextrins (CDs) belong to a class of cyclic oligosaccharides characterized by their toroidal shape consisting of glucose units linked via α-1,4-glycosidic bonds. This distinctive toroidal shape exhibits a dual nature, comprising a hydrophobic interior and a hydrophilic exterior, making CDs highly versatile in various pharmaceutical products. They serve multiple roles: they act as solubilizers, stabilizers, controlled release promoters, enhancers of drug bioavailability, and effective means of masking undesirable tastes and odors. Taking advantage of these inherent benefits, CDs have been integrated into numerous nanoscale drug delivery systems. The resulting nanomaterials exploit the exceptional properties of CDs, including their ability to solubilize hydrophobic drugs for substantial drug loading, engage in supramolecular complexation for engineered nanomaterials, increase bioavailability for improved therapeutic efficacy, stabilize labile drugs, and exhibit biocompatibility and versatility. This paper compiles recent studies on CD functional nanoscale drug delivery platforms. First, we described the physicochemical and toxicological aspects of CDs, CD/drug inclusion complexation, and their impact on improving drug bioavailability. We then summarized applications for CD-functional nano delivery systems based on polymeric, hybrid, lipid-based nanoparticles, and CD-based nanofibers. Particular interest was in the targeted applications and the function of the CD molecules used. In most applications, CD molecules were used for drug solubilization and loading, while in some studies, CD molecules were employed for supramolecular complexation to construct nanoscale drug delivery systems. Finally, the review concludes with a thoughtful consideration of the current challenges and outlook.

Functionalized composite nanofiber membranes for selective steroid hormone micropollutants uptake from water: Role of cyclodextrin type

Cyclodextrins (CD) entrapped in nanofiber composite membranes are potential selective adsorbing materials to remove steroid hormone (SHs) micropollutants from water. This study aims to elucidate the role of CD macrocyclic host type on the SHs inclusion complexation and uptake in filtration. Three CD types (α, β, and γ) are cross-linked with epichlorohydrin to form polymers (αCDP, βCDP and γCDP) and entrapped into a nanofiber composite membrane by electrospinning. TGA analysis confirmed the CD entrapment into the nanofiber without loss of CD molecules during filtration.The CD type plays a dominant role in controlling the removal of different SHs. A similar removal (range 33 to 50 %) was observed with αCDP, irrespective of the SH type. In contrast, removal and uptake dependent on SH type were observed for β and γCDP, with the highest removal of 74 % for progesterone, followed by estradiol (46 %) and estrone (27 %) and the lowest removal of 3 % for testosterone.Molecular dynamic (MD) simulation revealed a stronger and more stable complex formed with βCDP, as demonstrated by: i) the closer spatial distribution of SH molecules from the βCDP cavity and, ii) the quantum chemistry calculations of the lower de-solvation energy (+6.0 kcal/mol), which facilitates the release of water molecules from interacting interface of CD molecule and hormone. Regarding γCDP, the highest de-solvation energy (+8.3 kcal/mol) poses an energetic barrier, which hinders the formation of the inclusion complex. In the case of αCDP, a higher interaction energy (-8.9 kcal/mol) compared to βCDP (-4.9 kcal/mol) was obtained, despite the broader spatial distribution observed from the MD simulation attributed to a dominant hydrogen bonding interaction with the OH primary groups on the external surface cavity.The findings highlight the relevance of the CD type in designing selective adsorbing membranes for steroid hormone micropollutant uptake. Experimental results and MD simulation suggest that βCD is the most suitable CD type for steroid hormone uptake, due to a more stable and stronger inclusion complexation than α and γCD.

Size-tunable transmembrane nanopores assembled from decomposable molecular templates

Transmembrane nanopores, as key elements in molecular transport and single-molecule sensors, are assembled naturally from multiple monomers in the presence of lipid bilayers. The nanopore size, especially the precise diameter of the inner space, determines its sensing targets and further biological application. In this paper, we introduce a template molecule-aided assembly strategy for constructing size-tunable transmembrane nanopores. Inspired by the barrel-like structure, similar to many transmembrane proteins, cyclodextrin molecules of different sizes are utilized as templates and modulators to assemble the α-helical barreled peptide of polysaccharide transporters (Wza). The functional nanopores assembled by this strategy possess high biological and chemical activity and can be inserted into lipid bilayers, forming stable single channels for single-molecule sensing. After enzyme digestion, the cyclodextrins on protein nanopores can be degraded, and the remaining nontemplate transmembrane protein nanopores can also preserve the integrity of their structure and function. The template molecule-aided assembly strategy employed a simple and convenient method for fully artificially synthesizing transmembrane protein nanopores; the pore size is completely dependent on the size of the template molecule and controllable, ranging from 1.1 to 1.8 nm. Furthermore, by chemically synthesized peptides and modifications, the pore function is easily modulated and does not involve the cumbersome genetic mutations of other biological techniques.

2D-3D cyclodextrin-modified montmorillonite assembly for efficient directional capture of amines

Shale gas exploitation produces a large amount of waste liquid, which cannot be fully recovered and discharged. Discharged wastewater contains several chemicals, including petroleum hydrocarbons, salts, and heavy metals. Amine compounds can absorb harmful gases but may lead to the presence of these compounds in wastewater. Some amine compounds may cause DNA mutations and health threats to humans and animals. Inspired by the assembly of artificial two-dimensional structures, this paper attempts to shape montmorillonite (MMT) with a natural layered structure. Specifically, a functional 2D/3D amine compound collector within the limitations of 2D MMT (Mt) was prepared by self-assembling cyclodextrin molecules. With the assembly of cyclodextrin (CD) molecules, the two-dimensional Mt. layer length increased from 12.14 to 19.11 Å. Adsorption experiments revealed that functional MMT powder (FMP) has good trapping ability for amines, that the adsorption of amine groups on FMP decreases with increasing temperature, and that it has greater potential to remove amine compounds with fewer carbon chains. Through molecular dynamics simulation, it was found that there was a molecular binding energy between FMP and branched polyethyleneimine (BPEI), indicating that FMP had a spontaneous adsorption effect on BPEI. Furthermore, their adsorption favored the Langmuir isotherm model and the pseudo-second-order kinetic model. This study also provides a new collector for the total organic carbon (TOC) advanced treatment system. Compared with that of ozone and UV treatment, the removal rate of FMP is 10 times higher than that of activated carbon and active resin, which can better remove polar molecules and is beneficial for gas field water recovery.

Cyclodextrin Nanosponges: A Revolutionary Drug Delivery Strategy.

Nanosponges are porous solid cross-linked polymeric nanostructures. This study focuses on cyclodextrin-based nanosponges. Nanosponges based on cyclodextrin can form interactions with various lipophilic or hydrophilic compounds. The release of the entrapped molecules can be altered by altering the structure to obtain either a longer or faster release kinetics. The nanosponges might increase the aqueous solubility of weakly water-soluble compounds, develop long-lasting delivery systems, or construct novel drug carriers for nanomedicine. CD-NS (cyclodextrin-based nanosponges) are evolving as flexible and promising nanomaterials for medication administration, sensing, and environmental cleanup. CD-NS are three-dimensional porous structures of cyclodextrin molecules cross-linked by a suitable polymeric network, resulting in a large surface area. This overview covers CD-NS synthesis methods and applications.

Jellyfish-Inspired Self-Healing Luminescent Elastomers Based on Borate Nanoassemblies for Dual-Model Encryption.

Responsive luminescent materials that reversibly react to external stimuli have emerged as prospective platforms for information encryption applications. Despite brilliant achievements, the existing fluorescent materials usually have low information density and experience inevitable information loss when subjected to mechanical damage. Here, inspired by the hierarchical nanostructure of fluorescent proteins in jellyfish, we propose a self-healable, photoresponsive luminescent elastomer based on dynamic interface-anchored borate nanoassemblies for smart dual-model encryption. The rigid cyclodextrin molecule restricts the movement of the guest fluorescent molecules, enabling long room-temperature phosphorescence (0.37 s) and excitation wavelength-responsive fluorescence. The building of reversible interfacial bonding between nanoassemblies and polymer matrix together with their nanoconfinement effect endows the nanocomposites with excellent mechanical performances (tensile strength of 15.8 MPa) and superior mechanical and functional recovery capacities after damage. Such supramolecular nanoassemblies with dynamic nanoconfinement and interfaces enable simultaneous material functionalization and self-healing, paving the way for the development of advanced functional materials.

Cyclodextrin-assisted supramolecular host-guest inclusion for durable and sustainable optoelectronics

Metal halide perovskites and organic nonlinear optical materials have showcased enormous potential in many kinds of optoelectronic applications, such as solar cells, light-emitting diodes, and patterned displays. However, further enhancement of optoelectronic performances has been largely limited by the intractable issues of these materials including high defect densities, unstable crystallographic structure, harsh fabrication conditions, and unfavorable biocompatibility and environmental sustainability. Encouragingly, several recent works have demonstrated an effective supramolecular host-guest inclusion strategy could ideally address abovementioned concerns by nesting optoelectronic materials within the cavities of cyclodextrin molecules and their analogs. Specifically, the supramolecule hosts embedded with multiple functional groups and/or crosslinked networks could robustly interact with those optoelectronic materials, which play multifaceted roles in terms of chemical chelation, spatial confinement, structural stabilization, defect passivation, ion immobilization and compensation, thus resulting in comprehensive enhancement of optoelectronic performances and sustainability. The current challenging issues and potential solutions are also discussed to provide a roadmap for achieving more durable and sustainable optoelectronics toward practical applications and real commercialization.

The influence of cyclodextrin on hydrophobicity of pipeline and asphalt distribution: A green and efficient corrosion inhibitor

Corrosion inhibitors face significant limitations due to their non-degradability and poor applicability to asphalt systems. The molecular simulation studies show that cyclodextrin (CD) and asphalt can form supramolecular corrosion inhibitors with pipeline hydrophobic modification and corrosion inhibition effects. In particular, the rich hydroxyl structure of CD enables it to stably bind to the pipeline by forming coordination bonds and feedback bonds. When 2 CD molecules are added, the initial wetting time of the emulsion is delayed by 257.81 % compared to Span 80 with the same mass fraction. When 4 CD molecules are added, the emulsion cannot wet the iron surface within the simulation time. Furthermore, the combination of CD and asphalt allows more than 90 % of the asphalt to emulsify and prevent the emulsion from spreading on the pipeline. This results in a synergistic corrosion inhibition effect. These findings suggest that CD-based supramolecular corrosion inhibitors have the potential to be effective and environmentally friendly alternatives to traditional inhibitors in asphalt systems.

Synthesis of β-cyclodextrin derivatives substituted at larger or smaller rims via amine-catalyzed ring-opening oligomerization of ε-caprolactone

The involvement of cyclodextrins in transesterification reactions with active esters has been described to mimic enzyme-catalyzed reactions, making cyclodextrin molecules suitable as enzyme models. Cyclodextrin-catalyzed ring-opening of cyclic esters in bulk reaction conditions was considered to proceed similarly. However, the mechanism of activating cyclic esters through inclusion in the cyclodextrin cavity remains incompletely understood to date. The present research is focused on observing the transesterification of ε-caprolactone in the presence of β-cyclodextrin and additional amine organocatalysts within dimethyl sulfoxide solutions. The conducted experiments provide insights into the structural changes caused by various catalytic conditions in terms of the substitution pattern of the cyclodextrins. Our results are supported by a deep structural characterization through NMR and MALDI MS, which revealed the prospect of promoting rim-selective substitution of β-cyclodextrin at either secondary or primary hydroxyl groups using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) organocatalysts. This offers the possibility to prepare cyclodextrin derivatives with specific substitution patterns. Based on the acquired structural information, the particular pathway in which β-cyclodextrin influences the ring-opening of ε-caprolactone is delineated as follows: monomer complexation, substitution at the larger rim, chain elongation, and intramolecular transfer toward the smaller rim.

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.

Molecular simulations of doxorubicin complexed with native and modified cyclodextrins in water

In this study, all-atom molecular dynamics simulations have been performed to investigate from a nanoscopic point of view the interactions in supramolecular complexes formed between doxorubicin and cyclodextrins in an aqueous phase at a temperature of 310 K. All the simulations are on the time scales of microseconds and are carried out on High Performance Computing resources provided by the Greek Supercomputer ARIS. Doxorubicin, which is a well-known anticancer drug belonging to the class of anthracyclines, is simulated with two cyclodextrins of broad utilization in drug delivery, i.e.: γ-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. In both cases, the complexation process takes place spontaneously during the course of the simulations and a detailed analysis of the formed complexes is conducted in terms of structural, dynamical and thermodynamic properties. In addition, we present a quantitative analysis of how doxorubicin affects, upon complexation, the geometry, the hydrogen bonding network and the hydration of the selected cyclodextrins. Special attention is paid to the thermodynamic description of the simulated systems. More specifically, the standard binding free energy is calculated with an extended version of the linear interaction energy method. The presented in silico approach reveals that doxorubicin forms stable complexes with the chosen cyclodextrin molecules, there is a water solubility enhancement of the drug with respect to its unbound state and also cyclodextrins act protectively to the drug preventing undesired effects, such as the glycosidic degradation. Excellent agreement is found between the presented results and published in silico and experimental findings.

Stable nanometer-size beta-cyclodextrin – CeO2-x colloidal nanoparticles with high free radical scavenging activity

Cyclodextrin (CD) molecules are well-known for their ability to form inclusion complexes with hydrophobic molecules, including small drug molecules and lipophilic antioxidants. The combination of nanoparticles (NPs) with antioxidant properties (so-called nanozymes) and hydrophobic antioxidant molecules using CD@NP complexes can increase sufficiently the antioxidant efficiency of both components due to synergistic effect. Here we propose the new method of obtaining β-CD@CeO2-x complexes with addition of β-CD on the stage of syntheses of NPs. As a result, highly stable colloidal solutions of nanometer-size (2–3 nm) β-CD@CeO2-x nanoparticles were obtained. The stabilization effect of β-CD molecules was shown. Obtained β-CD@CeO2-x complexes reveal high antiradical activity in the number of experiments (including •OH and O2– scavenging) related to Ce3+/Ce4+ redox switching in nanoceria. The aggregation behavior of β-CD@CeO2-x complexes in various biological media was studied and the ways to improve their stability were proposed.

Supramolecular Self‐Assembled Nanospheres for Enzyme Encapsulation Based on Cyclodextrin

Based on the cyclodextrin (CD) and guest molecules inclusion, a novel rigid‐flexible polymeric nanosphere was prepared by supramolecular self‐assemble. The rigid part was formed by α‐cyclodextrin (α‐CD) and methoxypolyethylene glycol (mPEG) necklace‐like crystallites while the flexible part was sodium alginate (Alg). The rigid and flexible parts were linked by β‐cyclodextrin (β‐CD) and ferrocene (Fc) inclusion complex. This kind of nanosphere exhibited good glucose oxidase (GOD) encapsulation ability. The encapsulated enzyme, in comparison to the free enzyme, is able to retain its high activities across a rather broader range of pH, temperature, and time. After 20 days, the encapsulated enzyme can retain its almost 86% initial activity which exhibited good storage stability. These studies suggested that CD host‐guest inclusions to form stable polymeric nanospheres may be an effective way for enzyme encapsulation in various biomedical applications.

Eco-Conscious Approach to Thermoresponsive Star-Comb and Mikto-Arm Polymers via Enzymatically Assisted Atom Transfer Radical Polymerization Followed by Ring-Opening Polymerization.

This study explores the synthesis, characterization, and application of a heterofunctional initiator derived from 2-hydroxypropyl cyclodextrin (HP-β-CD), having eight bromoester groups and thirteen hydroxyl groups allowing the synthesis of mikto-arm star-shaped polymers. The bromoesterification of HP-β-CD was achieved using α-bromoisobutyryl bromide as the acylation reagent, modifying the cyclodextrin (CD) molecule as confirmed by electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR), attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy analysis, and differential scanning calorimetry (DSC) thermograms. The initiator's effectiveness was further demonstrated by obtaining star-comb and mikto-arm polymers via an enzymatically assisted atom transfer radical polymerization (ATRP) method and subsequent ring-opening polymerization (ROP). The ATR polymerization quality and control depended on the type of monomer and was optimized by the way of introducing the initiator into the reaction mixture. In the case of ATRP, high conversion rates for poly(ethylene oxide) methyl ether methacrylate (OEOMA), with molecular weights (Mn) of 500 g/mol and 300 g/mol, were achieved. The molecular weight distribution of the obtained polymers remained in the range of 1.23-1.75. The obtained star-comb polymers were characterized by different arm lengths. Unreacted hydroxyl groups in the core of exemplary star-comb polymers were utilized in the ROP of ε-caprolactone (CL) to obtain a hydrophilic mikto-arm polymer. Cloud point temperature (TCP) values of the synthesized polymers increased with arm length, indicating the polymers' reduced hydrophobicity and enhanced solvation by water. Atomic force microscopy (AFM) analysis revealed the ability of the star-comb polymers to create fractals. The study elucidates advancements in the synthesis and utilization of hydrophilic sugar-based initiators for enzymatically assisted ATRP in an aqueous solution for obtaining complex star-comb polymers in a controlled manner.

Cyclodextrins as Multi-Functional Ingredients in Dentistry.

Cyclodextrins are present in a variety of oral hygiene compositions. The present work describes the role of cyclodextrins in several toothpastes and mouthwashes that are already available in the market, as well as their prospective use in other applications as investigated in studies in the literature. Moreover, cyclodextrins are under study for the development of materials used in various techniques of dental repair, such as fillings, cements and binders therein. Their role in each of the innovative materials is presented. Finally, the prospect of the use of cyclodextrin-based delivery systems for the oral cavity is introduced, with a focus on new cyclodextrin molecules with dual action as bone-targeting agents and osteogenic drugs, and on new cross-linked cyclodextrin particles with a high drug loading and sustained drug delivery profile for the treatment of diseases that require prolonged action, such as periodontitis. In conclusion, cyclodextrins are herein demonstrated to act as versatile and multi-action ingredients with a broad range of applications in dentistry.

An Impedance-Based Approach for Sensing Cyclodextrin-Mediated Modulation of Membrane Cholesterol.

Cyclodextrin molecules are increasingly being used in biological research and as therapeutic agents to alter membrane cholesterol content, yet there is much to learn about their interactions with cell membranes. We present a biomembrane-based organic electronic platform capable of detecting interactions of cell membrane constituents with methyl-β-cyclodextrin (MβCD). This approach enables label-free sensing and quantification of changes in membrane integrity resulting from such interactions. In this work, we employ cholesterol-containing supported lipid bilayers (SLBs) formed on conducting polymer-coated electrodes to investigate how MβCD impacts membrane resistance. By examining the outcomes of MβCD interactions with SLBs of varying cholesterol content, we demonstrate that changes in membrane permeability or resistance can be used as a functional measure for predicting cyclodextrin-mediated cholesterol extraction from cellular membranes. Furthermore, we use the SLB platforms to electronically monitor cholesterol delivery to membranes following exposure to MβCD pre-loaded with cholesterol, observing that cholesterol enrichment is commensurate with an increase in resistance. This biomembrane-based bioelectronic sensing system offers a tool to quantify the modulation of membrane cholesterol content using membrane resistance and provides information regarding MβCD-mediated changes in membrane integrity. Given the importance of membrane integrity for barrier function in cells, such knowledge is essential for our fundamental understanding of MβCD as a membrane cholesterol modulator and therapeutic delivery vehicle.

Cyclodextrin - Essential Oil Complexes Studied by Thermal Gravimetry Analysis - Differential Scanning Calorimetry

Background: The structural features allow cyclodextrins to form solid inclusion complexes (host–guest complexes) with wide variety of solid, liquid, and gaseous compounds as a guest. It is the utmost an astounding property of the cyclodextrins, and is commonly termed as molecular recognition. The process of formation of an inclusion complex of the cyclodextrins has been associated with the substitution of the water inside the hydrophobic cavity and the non–covalent bonding interactions of the guest in the hydrophobic host cavity. Objective: To study the thermal gravimetry analysis behaviour for α–cyclodextrin–clove oil, α–cyclodextrin–neem oil and β–cyclodextrin–clove oil adducts using TGA–DSC. : To compute specific heat capacity at constant pressure, as a function of temperature for the studied systems. Methods: The thermal gravimetry analysis and differential scanning calorimetry techniques are used. Results: It is observed that the calculated Cp values from DSC curves are of low magnitude for α–CD–neem oil adduct as compared to that of individual constituents over the temperature range studied. An interesting pattern for the Cp values is found to emerge in case of α– CD–clove oil and β–CD–clove oil adducts wherein the calculated Cp values are higher in magnitude than for pure clove oil but are lower than that of the pure cyclodextrins. Conclusion: Using thermal methods, the attempt to understand the possibilities of molecular complex formation between cyclodextrins and medicinally important neem oil and clove oil is described. The crystals of inclusion compounds for clove oil and neem oil with α–CD and β–CD are synthesized. The results of TGA–DSC for the crystals are presented and analysed. Other: The results of neem oil–adducts have been explained in terms of binding of part of tri–glyceride linkages by 2–3 cyclodextrin molecules as neem oil is tri–glyceride and the adduct is having lower stability.

Recent Advances in the Pharmaceutical and Biomedical Applications of Cyclodextrin-Capped Gold Nanoparticles.

The real problem in pharmaceutical preparation is drugs' poor aqueous solubility, low permeability through biological membranes, and short biological t1/2. Conventional drug delivery systems are not able to overcome these problems. However, cyclodextrins (CDs) and their derivatives can solve these challenges. This article aims to summarize and review the history, properties, and different applications of cyclodextrins, especially the ability of inclusion complex formation. It also refers to the effects of cyclodextrin on drug solubility, bioavailability, and stability. Moreover, it focuses on preparing and applying gold nanoparticles (AuNPs) as novel drug delivery systems. It also studies the uses and effects of cyclodextrins in this field as novel drug carriers and targeting devices. The system formulated from AuNPs linked with CD molecules combines the advantages of both CD and AuNPs. Cyclodextrins benefit in increasing aqueous drug solubility, loading capacity, stability, and size control of gold NPs. Also, AuNPs are applied as diagnostic and therapeutic agents because of their unique chemical properties. Plus, AuNPs possess several advantages such as ease of detection, targeted and selective drug delivery, greater surface area, high loading efficiency, and higher stability than microparticles. In the present article, we tried to present the potential pharmaceutical applications of CD-derived AuNPs in biomedical applications including antibacterial, anticancer, gene-drug delivery, and various targeted drug delivery applications. Also, the article highlighted the role of CDs in the preparation and improvement of catalytic enzymes, the formation of self-assembling molecular print boards, the fabrication of supramolecular functionalized electrodes, and biosensors formation.

Abstract 710: Specific Removal Of Oxidized Cholesterol With A Cyclodextrin Dimer Drug Candidate Towards Reversing Atherosclerosis

Cardiovascular disease (CVD) is the world’s biggest killer. Current treatments for CVD are failing to deliver on promises to beat this deadly and complex family of diseases. New approaches that go beyond targeting LDL are needed. Cyclarity Therapeutics has developed a novel class of specifically engineered, dimerized cyclodextrin (CD) molecules for the encapsulation of toxic oxidized cholesterol. Oxidized cholesterol accumulates over time and causes dysfunction in many cell types, linking it to several age-related diseases including atherosclerosis. Presently, treatments for atherosclerosis are invasive, expensive, and/or show limited benefits. Here, a combination of in silico, in vitro, and ex vivo methods are used to implement a synergistic rational drug design strategy for developing CDs to remove atherogenic oxidized cholesterol (primarily 7-ketocholesterol (7KC)) from cells and tissues. Our results thus far indicate that our lead compound, UDP-003, can both prevent and reverse the formation of atherogenic foam cells in-vitro. UDP-003 binds and clears 7KC from in-vivo and ex-vivo systems selectivity. IND enabling studies, including pivotal GLP studies in rodent and non-rodent species, are complete and show that UDP-003 has an excellent safety profile with no significant clinical liabilities. UDP-003 has been awarded the Innovative Licensing and Access Pathway (ILAP) Innovation Passport by the MHRA, which is accelerating Cyclarity’s path to clinic and will facilitate rapid and innovative clinical trials. In totality, our data suggest that targeted removal of 7KC from foam cells with our proprietary class of cyclodextrin compounds has the potential to prevent and reverse the formation of atherosclerotic plaques. This innovation represents the first disease-modifying therapeutic approach to treating atherosclerotic disease.

Single-Particle Plasmonic Sensing of Nitric Oxide in Living Cells.

Plasmon resonance energy transfer (PRET), which occurs between plasmonic nanoparticles (NPs) and organic dyes, shows significant potential in sensing chemistry due to its high sensitivity at the single-particle level. In this work, a PRET-based sensing strategy was presented for the ultrasensitive sensing of nitric oxide (NO) in living cells. Supramolecular cyclodextrin (CD) molecules that exhibited different binding abilities to various molecules due to its unique rigid structure and annular cavity was applied and modified on gold NPs (GNPs) to construct the PRET nanosensors. NO-reactive molecules, rhodamine B-derived molecules (RdMs), were further inserted into the cavity of CD molecules through hydrophobic interactions to form host-guest structures. In the presence of NO, RdMs reacted with the target and generated rhodamine (RdB). Due to the spectral overlap between GNPs@CD and RdB molecules, PRET occurred and further led to a decrease in the scattering intensity of GNPs@CD, which was sensitive to the concentration of NO. The proposed sensing platform not only provides quantitative detection of NO in solution but also realized the single-particle imaging analysis of exogenous and endogenous NO in living cells. The single-particle plasmonic probes exhibit great potential in the in vivo sensing of biomolecules and metabolic processes.