International Journal of Molecular Sciences

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17 pages, 4800 KiB

Open AccessArticle

Mass Spectrometry, Ion Mobility Separation and Molecular Modelling: A Powerful Combination for the Structural Characterisation of Substituted Cyclodextrins Mixtures

by Sébastien Rigaud, Abdouramane Dosso, David Lesur, Dominique Cailleu, David Mathiron, Serge Pilard, Christine Cézard and Florence Djedaini-Pilard

Int. J. Mol. Sci. 2022, 23(21), 13352; https://doi.org/10.3390/ijms232113352 - 1 Nov 2022

Viewed by 2114

Abstract

When working on the synthesis of substituted cyclodextrins (CDs), the main challenge remains the analysis of the reaction media content. Our objective in this study was to fully characterise a complex isomers mixture of Lipidyl-βCDs (LipβCD) obtained with a degree of substitution 1 [...] Read more.

When working on the synthesis of substituted cyclodextrins (CDs), the main challenge remains the analysis of the reaction media content. Our objective in this study was to fully characterise a complex isomers mixture of Lipidyl-βCDs (LipβCD) obtained with a degree of substitution 1 (DS = 1) from a one-step synthesis pathway. The benefit of tandem mass spectrometry (MS/MS) and ion mobility separation hyphenated with mass spectrometry (IM-MS) was investigated. The MS/MS fragment ion‘s relative intensities were analysed by principal component analysis (PCA) to discriminate isomers. The arrival time distribution (ATD) of each isomer was recorded using a travelling wave ion mobility (TWIM) cell allowing the determination of their respective experimental collision cross section (CCS_exp). The comparison with the predicted theoretical CCS (CCS_th) obtained from theoretical calculations propose a regioisomer assignment according to the βCD hydroxyl position (2, 3, or 6) involved in the reaction. These results were validated by extensive NMR structural analyses of pure isomers combined with molecular dynamics simulations. This innovative approach seems to be a promising tool to elucidate complex isomer mixtures such as substituted cyclodextrin derivatives. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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8 pages, 1782 KiB

Open AccessArticle

Determination of Melting Parameters of Cyclodextrins Using Fast Scanning Calorimetry

by Askar K. Gatiatulin, Ivan A. Grishin, Aleksey V. Buzyurov, Timur A. Mukhametzyanov, Marat A. Ziganshin and Valery V. Gorbatchuk

Int. J. Mol. Sci. 2022, 23(21), 13120; https://doi.org/10.3390/ijms232113120 - 28 Oct 2022

Cited by 6 | Viewed by 1784

Abstract

The first evidence of native cyclodextrins fusion was registered using fast scanning calorimetry (FSC) with heating rates up to 40,000 K s⁻¹. The endothermal effects, detected at low heating rates, correspond to the decomposition processes. Upon the increase of the heating [...] Read more.

The first evidence of native cyclodextrins fusion was registered using fast scanning calorimetry (FSC) with heating rates up to 40,000 K s⁻¹. The endothermal effects, detected at low heating rates, correspond to the decomposition processes. Upon the increase of the heating rate the onset of these effects shifts to higher temperatures, reaching a limiting value at high heating rates. The limiting temperatures were identified as the melting points of α-, β- and γ-cyclodextrins, as the decomposition processes are suppressed at high heating rates. For γ-cyclodextrin the fusion enthalpy was measured. The activation energies of thermal decomposition of cyclodextrins were determined by dependence of the observed thermal effects on heating rates from 4 K min⁻¹ in conventional differential scanning calorimetry to 40,000 K s⁻¹ in FSC. The lower thermal stability and activation energy of decomposition of β-cyclodextrin than for the other two cyclodextrins were found, which may be explained by preliminary phase transition and chemical reaction without mass loss. The obtained values of fusion parameters of cyclodextrins are needed in theoretical models widely used for prediction of solubility and solution rates and in preparation of cyclodextrin inclusion compounds involving heating. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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14 pages, 4094 KiB

Open AccessArticle

Co-Formulation of Amphiphilic Cationic and Anionic Cyclodextrins Forming Nanoparticles for siRNA Delivery in the Treatment of Acute Myeloid Leukaemia

by Ayse Kont, Monique C. P. Mendonça, Michael F. Cronin, Mary R. Cahill and Caitriona M. O’Driscoll

Int. J. Mol. Sci. 2022, 23(17), 9791; https://doi.org/10.3390/ijms23179791 - 29 Aug 2022

Cited by 6 | Viewed by 2758

Abstract

Non-viral delivery of therapeutic nucleic acids (NA), including siRNA, has potential in the treatment of diseases with high unmet clinical needs such as acute myeloid leukaemia (AML). While cationic biomaterials are frequently used to complex the nucleic acids into nanoparticles, attenuation of charge [...] Read more.

Non-viral delivery of therapeutic nucleic acids (NA), including siRNA, has potential in the treatment of diseases with high unmet clinical needs such as acute myeloid leukaemia (AML). While cationic biomaterials are frequently used to complex the nucleic acids into nanoparticles, attenuation of charge density is desirable to decrease in vivo toxicity. Here, an anionic amphiphilic CD was synthesised and the structure was confirmed by Fourier-transform infrared spectroscopy (FT-IR), Nuclear Magnetic Resonance (NMR), and high-resolution mass spectrometry (HRMS). A cationic amphiphilic cyclodextrin (CD) was initially used to complex the siRNA and then co-formulated with the anionic amphiphilic CD. Characterisation of the co-formulated NPs indicated a significant reduction in charge from 34 ± 7 mV to 24 ± 6 mV (p < 0.05) and polydispersity index 0.46 ± 0.1 to 0.16 ± 0.04 (p < 0.05), compared to the cationic CD NPs. Size was similar, 161–164 nm, for both formulations. FACS and confocal microscopy, using AML cells (HL-60), indicated a similar level of cellular uptake (60% after 6 h) followed by endosomal escape. The nano co-formulation significantly reduced the charge while maintaining gene silencing (21%). Results indicate that blending of anionic and cationic amphiphilic CDs can produce bespoke NPs with optimised physicochemical properties and potential for enhanced in vivo performance in cancer treatment. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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9 pages, 7248 KiB

Open AccessArticle

NMR Investigation of the Supramolecular Complex Formed by a Phenylboronic Acid-Ferrocene Electroactive Probe and Native or Derivatized β-Cyclodextrin

by Andrea Cesari, Maria Antonietta Casulli, Takeshi Hashimoto and Takashi Hayashita

Int. J. Mol. Sci. 2022, 23(11), 6045; https://doi.org/10.3390/ijms23116045 - 27 May 2022

Cited by 2 | Viewed by 1764

Abstract

Specifically designed electrochemical sensors are standing out as alternatives to enzyme-based biosensors for the sensing of metabolites. In our previous works, we developed a new electrochemical assay based on cyclodextrin supramolecular complexes. A ferrocene moiety (Fc) was chemically modified by phenylboronic acid (4-Fc-PB) [...] Read more.

Specifically designed electrochemical sensors are standing out as alternatives to enzyme-based biosensors for the sensing of metabolites. In our previous works, we developed a new electrochemical assay based on cyclodextrin supramolecular complexes. A ferrocene moiety (Fc) was chemically modified by phenylboronic acid (4-Fc-PB) and combined with two different kinds of cyclodextrins (CDs): β-CD and β-CD modified by a dipicolylamine group (dpa-p-HB-β-CDs) for the sensing of fructose and adenosine-triphosphate (ATP), respectively. The aim of the present work is to better comprehend the features underlining the aforementioned complex formation. For the first time, a study about inclusion phenomena between the 4-Fc-PB electroactive probe with β-CD and with dpa-p-HB-β-CD was performed by using nuclear magnetic resonance (NMR) analysis. In particular, we focused on providing insights on the interaction involved and on the calculation of the binding constant of 4-Fc-PB/β-CD supramolecular complex, and elucidation about a drift in the time observed during the control experiments of the electrochemical measurements for the 4-Fc-PB/dpa-p-HB-β-CD supramolecular complex. In this sense, this paper represents a step further in the explanation of the electrochemical results obtained, pointing out the nature of the interactions present both in the formation of the inclusions and in the sensing with the analytes. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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26 pages, 4922 KiB

Open AccessArticle

Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects

by Kamil Wdowiak, Natalia Rosiak, Ewa Tykarska, Marcin Żarowski, Anita Płazińska, Wojciech Płaziński and Judyta Cielecka-Piontek

Int. J. Mol. Sci. 2022, 23(7), 4000; https://doi.org/10.3390/ijms23074000 - 4 Apr 2022

Cited by 28 | Viewed by 3362

Abstract

This study aimed at obtaining hesperidin (Hed) and hesperetin (Het) systems with HP-β-CD by means of the solvent evaporation method. The produced systems were identified using infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, in silico docking and [...] Read more.

This study aimed at obtaining hesperidin (Hed) and hesperetin (Het) systems with HP-β-CD by means of the solvent evaporation method. The produced systems were identified using infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, in silico docking and molecular dynamics studies were performed to assess the most preferable site of interactions between tested compounds and HP-β-CD. The changes of physicochemical properties (solubility, dissolution rate, and permeability) were determined chromatographically. The impact of modification on biological activity was tested in an antioxidant study as well as with regards to inhibition of enzymes important in pathogenesis of neurodegenerative diseases. The results indicated improvement in solubility over 1000 and 2000 times for Hed and Het, respectively. Permeability studies revealed that Hed has difficulties in crossing biological membranes, in contrast with Het, which can be considered to be well absorbed. The improved physicochemical properties influenced the biological activity in a positive manner by the increase in inhibitory activity on the DPPH radical and cholinoesterases. To conclude the use of HP-β-CD as a carrier in the formation of an amorphous inclusion complex seems to be a promising approach to improve the biological activity and bioavailability of Hed and Het. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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19 pages, 3257 KiB

Open AccessArticle

Solvent-Free Formation of Cyclodextrin-Based Pseudopolyrotaxanes of Polyethylene Glycol: Kinetic and Structural Aspects

by Nerea Guembe-Michel, Adrián Durán, Rafael Sirera and Gustavo González-Gaitano

Int. J. Mol. Sci. 2022, 23(2), 685; https://doi.org/10.3390/ijms23020685 - 8 Jan 2022

Cited by 2 | Viewed by 2401

Abstract

Pseudopolyrotaxanes (PPRs) are supramolecular structures consisting of macrocycles able to thread on a linear polymer chain in a reversible, non-covalent way, often referred to in the literature as “molecular necklaces”. While the synthesis and reaction mechanisms of these structures in solution have been [...] Read more.

Pseudopolyrotaxanes (PPRs) are supramolecular structures consisting of macrocycles able to thread on a linear polymer chain in a reversible, non-covalent way, often referred to in the literature as “molecular necklaces”. While the synthesis and reaction mechanisms of these structures in solution have been widely described, their solvent-free production has received little attention, despite the advantages that this route may offer. We propose in this work a kinetic mechanism that describes the PPR formation in the solid phase as a process occurring in two consecutive stages. This mechanism has been used to investigate the spontaneous formation of a PPR that occurs when grinding α-Cyclodextrin (α-CD) with polyethylene glycol (PEG). In the threading stage, the inclusion of the polymer and subsequent release of the water molecules lodged in the cavity of the macrocycle cause vibrational changes that are reflected in the time-dependence of the FTIR-ATR spectra, while the further assembly of PPRs to form crystals produces characteristic reflections in the XRD patterns, due to the channel-like arrangement of CDs, that can be used to track the formation of the adduct in crystalline form. The effects that working variables have on the kinetics of the reaction, such as temperature, feed ratio, molar mass of the polymer and the introduction of an amorphous block in the polymer structure, have been investigated. The rate constants of the threading step increase with the temperature and the activation energy of the process increases at lower proportions of CD to PEG. This is attributed to the lower degree of covering of the polymer chain with CDs that reduces the hydrogen-bonding driven stabilization between adjacent macrocycles. The formation of crystalline PPR, which takes place slowly at room temperature, is markedly promoted at higher temperatures, with lower proportions of CD favoring both the formation and the growth of the crystals. The molar mass of the polymer does not modify the typical channel-like arrangement of packed PPRs but the conversion into crystalline PPR diminishes when using PEG1000 instead of PEG400. At a microscopic level, the crystals arrange into lamellar structures, in the order of hundreds of nm, embedded in an amorphous-like matrix. The introduction of a polypropylene oxide block in the structure of the polymer (Pluronic L62) renders poorer yields and a considerable loss of crystallinity of the product of the reaction. The methodology here proposed can be applied to the general case of inclusion complexes of CDs with drugs in the solid phase, or to multicomponent systems that contain polymers as excipients in pharmaceutical formulations along with CDs. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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26 pages, 6628 KiB

Open AccessArticle

Preparation, Characterization and Evaluation of the Anti-Inflammatory Activity of Epichlorohydrin-β-Cyclodextrin/Curcumin Binary Systems Embedded in a Pluronic^®/Hyaluronate Hydrogel

by Ana-María Fernández-Romero, Francesca Maestrelli, Sara García-Gil, Elena Talero, Paola Mura, Antonio M. Rabasco and María Luisa González-Rodríguez

Int. J. Mol. Sci. 2021, 22(24), 13566; https://doi.org/10.3390/ijms222413566 - 17 Dec 2021

Cited by 11 | Viewed by 3407

Abstract

Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-β-CD (EpiβCD) was used as polymeric CD. [...] Read more.

Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-β-CD (EpiβCD) was used as polymeric CD. To characterize the binary system, solid-state and in-solution studies were performed. Afterwards, an experimental design was performed to optimize the hydrogel system. Finally, the CurEpiβCD hydrogel system was tested for anti-inflammatory activity using a HaCat psoriasis cell model. Co-grinded Cur/EpiβCD binary system showed a strong interaction and Curcumin solubility was much improved. Its combination with Pluronic^® F-127/hyaluronate hydrogel demonstrated an improvement in release rate and Curcumin permeation. After testing its anti-inflammatory activity, the system showed a significant reduction in IL-6 levels. Hydrogel-containing CurEpiβCD complex is a great alternative to treat topical inflammatory diseases. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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14 pages, 1668 KiB

Open AccessArticle

Increase in the Antioxidant and Anti-Inflammatory Activity of Euterpe oleracea Martius Oil Complexed in β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin

by Thalita Sévia Soares de Almeida Magalhães, Pollyana Cristina de Oliveira Macedo, Érika Cibely Pinheiro da Costa, Emanuella de Aragão Tavares, Valéria Costa da Silva, Gerlane Coelho Bernardo Guerra, Joquebede Rodrigues Pereira, Telma Maria de Araújo Moura Lemos, Marília Medeiros Fernandes de Negreiros, Hugo Alexandre de Oliveira Rocha, Attilio Converti and Ádley Antonini Neves de Lima

Int. J. Mol. Sci. 2021, 22(21), 11524; https://doi.org/10.3390/ijms222111524 - 26 Oct 2021

Cited by 4 | Viewed by 2231

Abstract

Reactive oxygen species (ROS) are aerobic products generated during cellular respiration, but in the case of oxidative stress, they become key factors in the development of inflammatory processes and chronic diseases such as diabetes and rheumatoid arthritis. In this work, Euterpe oleracea oil [...] Read more.

Reactive oxygen species (ROS) are aerobic products generated during cellular respiration, but in the case of oxidative stress, they become key factors in the development of inflammatory processes and chronic diseases such as diabetes and rheumatoid arthritis. In this work, Euterpe oleracea oil (EOO), as well as the complexes produced by slurry (S) and kneading (K), were analyzed for antioxidant capacity in vitro, while only the β-cyclodextrin complex obtained by kneading (EOO-βCD-K), which showed better complexation, was selected for anti-inflammatory assays in vivo. In the scavenging activity of OH·, the hydroxypropyl-β-cyclodextrin complex obtained by kneading (EOO-HPβCD-K) exhibited an activity 437% higher than the pure oil. In the paw edema assay, EOO-βCD-K reduced edema by 200% and myeloperoxidase (MPO) activity by 112%. In an air pouch model, this treatment showed a reduction in leukocyte, MPO, and Interleukin-1β (IL-1β) levels; meanwhile those of glutathione and IL-10 were increased, demonstrating its ability to potentiate the anti-inflammatory effect of EOO. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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19 pages, 9341 KiB

Open AccessArticle

Cyclodextrin Nanosponges Inclusion Compounds Associated with Gold Nanoparticles for Potential Application in the Photothermal Release of Melphalan and Cytoxan

by Sebastián Salazar, Nicolás Yutronic, Marcelo J. Kogan and Paul Jara

Int. J. Mol. Sci. 2021, 22(12), 6446; https://doi.org/10.3390/ijms22126446 - 16 Jun 2021

Cited by 16 | Viewed by 2876

Abstract

This article describes the synthesis and characterization of β-cyclodextrin-based nano-sponges (NS) inclusion compounds (IC) with the anti-tumor drugs melphalan (MPH) and cytoxan (CYT), and the addition of gold nanoparticles (AuNPs) onto both systems, for the potential release of the drugs by means of [...] Read more.

This article describes the synthesis and characterization of β-cyclodextrin-based nano-sponges (NS) inclusion compounds (IC) with the anti-tumor drugs melphalan (MPH) and cytoxan (CYT), and the addition of gold nanoparticles (AuNPs) onto both systems, for the potential release of the drugs by means of laser irradiation. The NS-MPH and NS-CYT inclusion compounds were characterized using scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), energy dispersive spectroscopy (EDS), thermogravimetric analysis (TGA), UV–Vis, and proton nuclear magnetic resonance (¹H-NMR). Thus, the inclusion of MPH and CYT inside the cavities of NSs was confirmed. The association of AuNPs with the ICs was confirmed by SEM, EDS, TEM, and UV–Vis. Drug release studies using NSs synthesized with different molar ratios of β-cyclodextrin and diphenylcarbonate (1:4 and 1:8) demonstrated that the ability of NSs to entrap and release the drug molecules depends on the crosslinking between the cyclodextrin monomers. Finally, irradiation assays using a continuous laser of 532 nm showed that photothermal drug release of both MPH and CYT from the cavities of NSs via plasmonic heating of AuNPs is possible. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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23 pages, 4967 KiB

Open AccessArticle

Robust Ruthenium Catalysts Supported on Mesoporous Cyclodextrin-Templated TiO₂-SiO₂ Mixed Oxides for the Hydrogenation of Levulinic Acid to γ-Valerolactone

by Cédric Decarpigny, Sébastien Noël, Ahmed Addad, Anne Ponchel, Eric Monflier and Rudina Bleta

Int. J. Mol. Sci. 2021, 22(4), 1721; https://doi.org/10.3390/ijms22041721 - 9 Feb 2021

Cited by 2 | Viewed by 2765

Abstract

In this paper, we present a versatile template-directed colloidal self-assembly method for the fabrication in aqueous phase of composition-tuned mesoporous RuO₂@TiO₂-SiO₂ catalysts. Randomly methylated β-cyclodextrin/Pluronic F127 supramolecular assemblies were used as soft templates, TiO₂ colloids as building [...] Read more.

In this paper, we present a versatile template-directed colloidal self-assembly method for the fabrication in aqueous phase of composition-tuned mesoporous RuO₂@TiO₂-SiO₂ catalysts. Randomly methylated β-cyclodextrin/Pluronic F127 supramolecular assemblies were used as soft templates, TiO₂ colloids as building blocks, and tetraethyl orthosilicate as a silica source. Catalysts were characterized at different stages of their synthesis using dynamic light scattering, N₂-adsorption analysis, powder X-ray diffraction, temperature programmed reduction, high-resolution transmission electron microscopy, high-angle annular bright-field and dark-field scanning transmission electron microscopy, together with EDS elemental mapping. Results revealed that both the supramolecular template and the silica loading had a strong impact on the pore characteristics and crystalline structure of the mixed oxides, as well as on the morphology of the RuO₂ nanocrystals. Their catalytic performance was then evaluated in the aqueous phase hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) under mild conditions (50 °C, 50 bar H₂). Results showed that the cyclodextrin-derived catalyst displayed almost quantitative LA conversion and 99% GVL yield in less than one hour. Moreover, this catalyst could be reused at least five times without loss of activity. This work offers an effective approach to the utilization of cyclodextrins for engineering the surface morphology of Ru nanocrystals and pore characteristics of TiO₂-based materials for catalytic applications in hydrogenation reactions. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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18 pages, 3759 KiB

Open AccessArticle

Controlled Drug Release and Cytotoxicity Studies of Beta-Lapachone and Doxorubicin Loaded into Cyclodextrins Attached to a Polyethyleneimine Matrix

by Agata Kowalczyk, Artur Kasprzak, Magdalena Poplawska, Monika Ruzycka, Ireneusz P. Grudzinski and Anna M. Nowicka

Int. J. Mol. Sci. 2020, 21(16), 5832; https://doi.org/10.3390/ijms21165832 - 14 Aug 2020

Cited by 5 | Viewed by 3086

Abstract

This work presents a new look at the application of cyclodextrins (CD) as a drug nanocarrier. Two different cyclodextrins (αCD, βCD) were covalently conjugated to branched polyethylenimine (PEI), which was additionally functionalized with folic acid (PEI-βCD-αCD-FA). [...] Read more.

This work presents a new look at the application of cyclodextrins (CD) as a drug nanocarrier. Two different cyclodextrins (αCD, βCD) were covalently conjugated to branched polyethylenimine (PEI), which was additionally functionalized with folic acid (PEI-βCD-αCD-FA). Here, we demonstrated that the combination of αCD and βCD enabled to load and control release of two anticancer drugs: doxorubicin (DOX) and beta-lapachone (beta-LP) (DOX in β-CD and beta-LP into α-CD) via host-guest inclusion. The PEI-βCD(DOX)-αCD-FA nanoconjugate was used to transport anticancer drugs into A549 lung cancer cells for estimation the cytotoxic and antitumor effect of this nanoconjugate. The presence of FA molecules should facilitate the penetration of studied nanoconjugate into the cell. Whereas, the non-cellular experiments proved that the drugs are released from the carrier mainly in the pH 4.0. The release mechanism is found to be anomalous in all studied cases. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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19 pages, 3037 KiB

Open AccessArticle

Intracellular Fate and Impact on Gene Expression of Doxorubicin/Cyclodextrin-Graphene Nanomaterials at Sub-Toxic Concentration

by Daniela Caccamo, Monica Currò, Riccardo Ientile, Elisabetta AM Verderio, Angela Scala, Antonino Mazzaglia, Rosamaria Pennisi, Maria Musarra-Pizzo, Roberto Zagami, Giulia Neri, Consolato Rosmini, Monica Potara, Monica Focsan, Simion Astilean, Anna Piperno and Maria Teresa Sciortino

Int. J. Mol. Sci. 2020, 21(14), 4891; https://doi.org/10.3390/ijms21144891 - 10 Jul 2020

Cited by 18 | Viewed by 3391

Abstract

The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we [...] Read more.

The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString^® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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Review

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21 pages, 1634 KiB

Open AccessReview

Cyclodextrin-Based Polymeric Materials Bound to Corona Protein for Theranostic Applications

by Donya Esmaeilpour, Jens Albert Broscheit and Sergey Shityakov

Int. J. Mol. Sci. 2022, 23(21), 13505; https://doi.org/10.3390/ijms232113505 - 4 Nov 2022

Cited by 4 | Viewed by 2851

Abstract

Cyclodextrins (CDs) are cyclic oligosaccharide structures that could be used for theranostic applications in personalized medicine. These compounds have been widely utilized not only for enhancing drug solubility, stability, and bioavailability but also for controlled and targeted delivery of small molecules. These compounds [...] Read more.

Cyclodextrins (CDs) are cyclic oligosaccharide structures that could be used for theranostic applications in personalized medicine. These compounds have been widely utilized not only for enhancing drug solubility, stability, and bioavailability but also for controlled and targeted delivery of small molecules. These compounds can be complexed with various biomolecules, such as peptides or proteins, via host-guest interactions. CDs are amphiphilic compounds with water-hating holes and water-absorbing surfaces. Architectures of CDs allow the drawing and preparation of CD-based polymers (CDbPs) with optimal pharmacokinetic and pharmacodynamic properties. These polymers can be cloaked with protein corona consisting of adsorbed plasma or extracellular proteins to improve nanoparticle biodistribution and half-life. Besides, CDs have become famous in applications ranging from biomedicine to environmental sciences. In this review, we emphasize ongoing research in biomedical fields using CD-based centered, pendant, and terminated polymers and their interactions with protein corona for theranostic applications. Overall, a perusal of information concerning this novel approach in biomedicine will help to implement this methodology based on host-guest interaction to improve therapeutic and diagnostic strategies. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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35 pages, 1321 KiB

Open AccessReview

Application of Molecular Dynamics Simulations in the Analysis of Cyclodextrin Complexes

by Anna Helena Mazurek, Łukasz Szeleszczuk and Tomasz Gubica

Int. J. Mol. Sci. 2021, 22(17), 9422; https://doi.org/10.3390/ijms22179422 - 30 Aug 2021

Cited by 54 | Viewed by 6054

Abstract

Cyclodextrins (CDs) are highly respected for their ability to form inclusion complexes via host–guest noncovalent interactions and, thus, ensofance other molecular properties. Various molecular modeling methods have found their applications in the analysis of those complexes. However, as showed in this review, molecular [...] Read more.

Cyclodextrins (CDs) are highly respected for their ability to form inclusion complexes via host–guest noncovalent interactions and, thus, ensofance other molecular properties. Various molecular modeling methods have found their applications in the analysis of those complexes. However, as showed in this review, molecular dynamics (MD) simulations could provide the information unobtainable by any other means. It is therefore not surprising that published works on MD simulations used in this field have rapidly increased since the early 2010s. This review provides an overview of the successful applications of MD simulations in the studies on CD complexes. Information that is crucial for MD simulations, such as application of force fields, the length of the simulation, or solvent treatment method, are thoroughly discussed. Therefore, this work can serve as a guide to properly set up such calculations and analyze their results. Full article

(This article belongs to the Special Issue Recent Insights in Chemistry and Technology of Cyclodextrins)

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