Cyclodextrin-based supramolecular nanogels decorated with mannose for short peptide encapsulation.

Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a straightforward technique to fabricate a novel class of physically cross-linked nanogels via a self-assembly process in water involving α-cyclodextrin and a mannose molecule that was hydrophobically modified using an alkyl chain. The alkyl chain-modified mannose was synthesized in five steps, starting with D-mannose. Subsequently, nanogels were formed by subjecting α-cyclodextrin and the hydrophobically modified mannose to magnetic stirring in water. By adjusting the mole ratio between the hydrophobically modified mannose and α-cyclodextrin, nanogels with an average 100-150 nm diameter were obtained. Physicochemical and structural analyses by 1H NMR and X-ray diffraction unveiled a supramolecular and hierarchical mechanism underlying the creation of these nanogels. The proposed mechanism of nanogel formation involves two distinct steps: initial interaction of hydrophobically modified mannose with α-cyclodextrin resulting in the formation of inclusion complexes, followed by supramolecular interactions among these complexes, ultimately leading to nanogel formation after 72 h of stirring. We demonstrated the nanogels' ability to encapsulate a short peptide ([p-tBuF2, R5]SHf) as a water-soluble drug model. This discovery holds promise for potentially utilizing these nanogels in drug delivery applications.

Nickel sulfide and dysprosium-doped nickel sulfide nanoparticles: Dysprosium-induced variation in properties, in vitro chemo-photothermal behavior, and antibacterial activity.

Newer materials for utilization in multi-directional therapeutic actions are investigated, considering delicate design principles involving size and shape control, surface modification, and controllable drug loading and release. Multi-faceted properties are imparted to the engineered nanoparticles, like magnetism, near-infrared absorption, photothermal efficiency, and suitable size and shape. This report presents nickel sulfide and dysprosium-doped nickel sulfide nanoparticles with poly-ß-cyclodextrin polymer coating. The nanoparticles belong to the orthorhombic crystal systems, as indicated by X-ray diffraction studies. The size and shape of the nanoparticles are investigated using Transmission Electron Microscope (TEM) and a particle-size analyzer. The particles show soft ferromagnetic characteristics with definite and moderate saturation magnetization values. The nickel sulfide nanoparticles' in vitro anticancer and antibacterial activities are investigated in free and 5-fluorouracil/penicillin benzathine-loaded forms. The 5-fluorouracil-encapsulation efficiency of the nanoparticles is around 87%, whereas it is above 92% in the case of penicillin benzathine. Both drugs are released slowly in a controlled fashion. The dysprosium-doped nickel sulfide nanoparticles show better anticancer activity, and the efficacy is more significant than the free drug. The nanoparticles are irradiated with a low-power 808 nm laser. The dysprosium-doped nickel sulfide nanoparticles attain a higher temperature on irradiation, i.e., above 59 °C. The photothermal conversion efficiency of this material is determined, and the significance of dysprosium doping is discussed. Contrarily, the undoped nickel sulfide nanoparticles show more significant antibacterial activity. This study presents a novel designed nanoparticle system and the exciting variation of properties on dysprosium doping in nickel sulfide nanoparticles.

Interaction of the platinum complex of tyrosine-ß-cyclodextrin with G-quadruplex DNA.

The telomeric quadruplex structures formed by the guanine-rich sequences of DNA have emerged as targets for small molecules designed and synthesized to stabilize the G-quadruplexes. This report presents a newly synthesized tyrosine-tethered cyclodextrin derivative and its platinum complex. Their structures are characterized using IR, NMR, and mass spectral techniques. The binding interactions of the platinum complex with CT-DNA and the kit22, myc22, and telo24 G-quadruplexes are investigated employing absorption and fluorescence spectral titrations. The binding constant or KSV values of the interaction with the G-quadruplexes are more significant than those with the duplex DNA by order of 10. It presents the compound as a G-quadruplex-selective binder. Further, the well-known G-quadruplex binding molecule Berberine is encapsulated in the Tyr- ß-CD through a host: guest association. The structure of the host: guest complex is investigated employing 2D ROESY spectroscopy. In addition, the study on the binding interaction of the complex to the DNA targets is also carried out. The mode and strength of interaction of the free and the Berberine-loaded Tyr-ß-CD to the duplex and the quadruplexes are reported.

Differential interaction of Fluorescein-ß-cyclodextrin conjugate to quadruplex kit22 DNA: Inclusion of Berberine and modulation of binding.

Clinical applicability of G-quadruplexes as anticancer drugs is an area of current interest. Identification of supramolecular systems for selective targeting G-quartets is particularly intriguing. In this work, the DNA binder Berberine is encapsulated inside the molecular cavity of the synthesised host structure, Fluoresecein-ß-cyclodextrin conjugate. The host: guest complex is characterized and the mode of binding is optimized using two dimensional rotating-frame Overhauser effect spectroscopy. The conjugate is examined for its binding to quadruplex DNAs viz., kit22, myc22, telo24 and the duplex calf-thymus DNA before and after Berberine encapsulation. UV-vis and fluorescence spectroscopic methods were employed to determine the strength of binding of the complex with the DNAs. The binding strength and the stoichiometry of the host: guest complex are 1.9 × 106 mol-1 dm3 and 1:1, respectively. A quenching of fluorescence of the quadruplex kit22 and duplex ctDNA is observed on binding to the Fluorescein-ß-cyclodextrin conjugate. The quadruplexes of myc22 and telo24 display an enhanced fluorescence on binding to the modified cyclodextrin. The Stern-Volmer quenching constants are 1.4 × 106 mol-1 dm3 and 3.8 × 105 mol-1 dm3 for binding to kit22 and ctDNA respectively. kit22 shows a different emission profile on interacting with the Berberine encapsulated conjugate, whereas all the other quadruplexes and duplex exhibit similar emission profiles. The results indicate a variation in the binding mode and strength of the ligand-quadruplexes and depend on the conformation of the quadruplexes.Communicated by Ramaswamy H. Sarma.

Affinity variation in the interactions of tryptophan- ß-cyclodextrin-platinum complex with G-quadruplex and duplex DNAs.

DNA forms non-canonical Guanine-rich-quadruplex structures that play crucial roles such as maintenance of the telomere, transcription, and replication. Selective binding of small molecular ligands to G-quadruplexes and stabilization of them gain importance in the control of cell proliferation and development of therapeutics. In this paper, we report the synthesis of a tryptophan-ß-cyclodextrin complex and its platinum complex. The binding interaction of the synthesized Trp-ß-CD-Pt compound with various DNAs, including a duplex DNA and three quadruplexes, are investigated. The binding of the compound to quadruplexes shows a general increase in the binding strength compared to the strength of binding with the duplex, CT-DNA. The compound reveals the strongest binding with kit22. An enhancement of fluorescence is generally observed when the ligand binds to all the DNAs, except myc22. The structure of the host: guest complex with Berberine, a model G-quadruplex binding ligand, is investigated using 2 D ROESY spectroscopy. The host: guest binding is strong and the DNA interaction does not extract much of the Berberine molecule from the complex. The differential bindings of the ligand in free- and Berberine-loaded forms with different G-quadruplexes are discussed in detail based on binding strengths and the modulation of fluorescence.Communicated by Ramaswamy H. Sarma.

Poly-ß-Cyclodextrin-coated neodymium-containing copper sulphide nanoparticles as an effective anticancer drug carrier.

This study aims at tuning the properties of the nanoparticles by incorporating neodymium, exploring the sustained release of drug, and the anticancer activity on breast cancer cells. The crystal characteristics of NdCuS2 nanoparticles are analysed using X-ray diffraction. The morphology and size of the nanoparticles were characterised using Transmission Electron Microscope and particle size analyser. The rate of release of the encapsulated camptothecin and anticancer effects on breast cancer cells are investigated. The nanoparticles are rod-shaped, 132 ± 8 nm long and 27 ± 7 nm wide. The band gap of the nanoparticles is 4.85 eV. The drug encapsulation efficiency is 94.76% (w/w). The drug is released in a sustained manner, over a period of 180 h. The cytotoxicity of the camptothecin-loaded NPs is examined on MDA-MB-231 cells and the IC50 is 4.39 µg mL-1. The NdCuS2 nanoparticles are promising as theranostic agents considering their material characteristics and anticancer activity.

Molecular encapsulation of berberine and ethidium bromide in anthraquinonecarboxamido-ß-cyclodextrin conjugate: supramolecular association with DNA duplex and G-quadruplexes.

G-quadruplex DNA in recognized as a potential target for anti-cancer drugs. In this work, an anthraquinonecarboxamido derivative of ß-cyclodextrin (AQCC) is synthesized as a novel DNA binder that further can deliver an additional molecule at the target, carrying it in the cavity of modified cyclodextrin. The binding of AQCC with ethidium bromide (EtBr), berberine (Ber), duplex calf-thymus DNA (CT-DNA), quadruplexes (G4) viz., kit22, myc22, and telo24 are studied. The compound acts as a host molecule for the encapsulation of DNA binders viz., EtBr, Ber and enhances their fluorescence due to the encapsulation in its AQCC's cyclodextrin cavity. The binding constant of the host: guest complex of EtBr and Ber with AQCC's cavity are 6.4 × 105 and 3.3 × 106 mol-1 dm3, respectively. The proximity of the protons of the guest and host molecules is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY). The conjugate displays a quenching of fluorescence selectively on the association with CT-DNA and quadruplex kit22 that is contrast to the spectral behavior with quadruplex myc22 and telo24. CT-DNA exhibits dissimilar fluorescence spectra in free- and EtBr-bound forms. In addition, kit22 exhibit dissimilar emission profile when AQCC encapsulates Ber. Therefore, the Ber-loaded complexes and the AQCC molecule bind to different G-quadruplexes with different binding strengths. In addition, the effect of Ber in binding to the target DNAs is pronounces since the Ber molecule has more affinity to bind to quadruplexes than the duplex.