Engineered praseodymium sulfide nanocarrier and supramolecular association of anticancer drug for effective delivery to breast cancer cells.

Metal sulfide nanoparticles are synthesized for their biomedical applications, including cancer drug targeting. This paper reports a novel nanocomposite made of praseodymium sulfide nanoparticles and poly-cyclodextrin. The praseodymium sulfide nanoparticles were synthesized hydrothermal, autoclaving the nitrate precursors at 150 °C for 18 hours. The material is characterized using XRD and shows an orthorhombic crystal system with high crystallinity. The size and morphology of the nanomaterial were optimized. The material shows a rod-shaped morphology, as seen in the TEM image, with 150 ± 3 nm length and 25 ± 5 nm width. Particle size analysis supports this size range. The colloidal particles were stable in the aqueous medium without precipitation at neutral pH. The elements in the material in the polymer-coated form and their electronic states are studied by X-ray photoelectron spectroscopy. Thermogravimetry confirms that the material contains about 18.5% of the weight of the polymer. The material has an observable magnetic property at room temperature due to the praseodymium element. The UV-vis-NIR absorption spectrum of the material shows a long absorption range that extends to 1200 nm. The drug 5-fluorouracil is encapsulated in the nanoparticles through host: guest association, and its release profile is analyzed. The release is modulated at a slightly acidic pH, indicating the pH-tunability. The nanoparticles and 5-fluorouracil were taken in the w/w ratio of 2:1 (2/1 mg in 1 mL of deionized water). Further, the in vitro anticancer activity of the drug-encapsulated material is screened on breast cancer and non-cancerous cell lines. The IC50 values are reported, and the advantageous properties of the material as drug carriers are discussed.

Dysprosium-containing cobalt sulfide nanoparticles as anticancer drug carriers.

BACKGROUND: Among various materials designed for anticancer drug transport, sulfide nanoparticles are uniquely intriguing owing to their spectral characteristics. Exploration of newer nanoscale copper sulfide particles with dysprosium doping is reported herein. It leads to a change in the physicochemical properties of the sulfide nanoparticles and hence the difference in drug release and cytotoxicity. OBJECTIVE: We intend to purport the suitably engineered cobalt sulfide and dysprosium-doped cobalt sulfide nanoparticles that are magnetic and NIR-absorbing, as drug delivery vehicles. The drug loading and release are based on the supramolecular drug complex formation on the surface of the nanoparticles. METHOD: The nanomaterials are synthesized employing hydrothermal procedures, coated with a biocompatible poly-ß-cyclodextrin, and characterized using the methods of diffractometry, microscopy, spectroscopy, thermogravimetry and magnetometry. The sustained drug release is investigated in vitro. 5-Fluorouracil is loaded in the nanocarriers. The empty and 5-fluorouracil-loaded nanocarriers are screened for their anti-breast cancer activity in vitro on MCF-7 cells. RESULTS: The size of the nanoparticles is below 10 nm. They show soft ferromagnetic characteristics. Further, they show broad NIR absorption bands extending up to 1200 nm, with the dysprosium-doped material displaying greater absorbance. The drug 5-fluorouracil is encapsulated in the nanocarriers and released sustainably, with the expulsion duration extending over 10 days. The IC50 of the blank and the drug-loaded cobalt sulfide are 16.24 ± 3.6 and 12.2 ± 2.6 µg mL-1, respectively. For the drug-loaded, dysprosium-doped nanocarrier, the IC50 value is 9.7 ± 0.3 µg mL-1. CONCLUSION: The ultrasmall nanoparticles possess a size suitable for drug delivery and are dispersed well in the aqueous medium. The release of the loaded 5-fluorouracil is slow and sustained. The anticancer activity of the drug-loaded nanocarrier shows an increase in efficacy, and the cytotoxicity is appreciable due to the controlled release. The nanocarriers show multi-functional characteristics, i.e., magnetic and NIR-absorbing, and are promising drug delivery agents.

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.

G-Quadruplex selectivity and cytotoxicity of a guanidine-encapsulated porphyrin-cyclodextrin conjugate.

G-Quadruplex DNAs represent out-of-the-way nucleic acid conformations, frequently formed by guanine-rich sequences. They have emanated as cancer-associated targets for designed small molecules. The variation in the binding affinity of the synthesized compounds to duplex and quadruplex structures is an intriguing quest, solved by spectroscopic analysis. In this paper, we report the synthesis of a porphyrin-cyclodextrin conjugate, characterized by utilizing FT-IR, NMR, and mass spectrometry. Further, two benzimidazolylguanidines are synthesized which form host: guest complexes with the porphyrin-cyclodextrin conjugate. The structure of the complexes is optimized by analyzing their 2D ROESY spectra. The interactions of the host, guest, and the host: guest complexes with the duplex (calf thymus DNA) and quadruplex (kit22) nucleic acids are investigated employing UV-vis, fluorescence, circular dichroism, and DNA melting experiments. The calculated strengths of the compounds' binding with kit22 are in the order of 106, which is larger than those observed for the duplex DNA binding. The significant G-quadruplex selectivity of the host: guest complex of anthracenyl-benzimidazolylguanidine is discussed in detail. Further, the in vitro cytotoxicity of the compounds on MCF-7 cell lines is examined. The host: guest complexes show enhanced half-maximal inhibitory concentration values compared to the un-complexed compounds.

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.

G-Quadruplex binding of cavity-containing anthraquinonesulfonyl-ß-cyclodextrin conjugate. Effect of encapsulation of ethidium bromide and berberine.

An anthraquinonesulfonyl derivative of ß-cyclodextrin is prepared and characterized employing spectroscopic techniques. The binding interactions of the compound with ethidium bromide, berberine, calf-thymus DNA, quadruplex DNAs viz., kit22, telo24, and myc22 are investigated by ultraviolet-visible, and fluorescence spectroscopic methods. Anthraquinonesulfonyl-ß-cyclodextrin conjugate acts as a host molecule and enhances ethidium bromide and berberine fluorescence due to their encapsulation in cyclodextrin's cavity. The binding constant values are 9.0 × 105 mol-1 dm3 and 5.7 × 104 mol-1 dm3 for the formation of host: guest complexes of the ß-CD derivative with ethidium bromide and berberine respectively. The proximity of the protons of ethidium bromide and berberine protons with those of the internal cavity of ß-CD in the anthraquinonesulfonyl-ß-CD conjugate is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy. The conjugate displays a quenching of fluorescence selectively to the quadruplexes kit22 and telo24 that is contrast to the spectral behavior with duplex DNA. ctDNA and myc22 exhibit different absorption and emission profiles with ethidium bromide on encapsulation by ß-CD. The encapsulation of berberine leads to a fluorescence enhancement on binding to ctDNA, telo24, and myc22 with binding constants of 5.6 × 105, 3.3 × 105 mol-1 dm3, and 1.5 × 105 mol-1 dm3 respectively. In contrast, kit22 leads to fluorescence quenching on berberine encapsulated-anthraquinonesulfonyl-ß-cyclodextrin conjugate with a Stern-Volmer constant of 3.3 × 105 mol-1 dm3.Communicated by Ramaswamy H. Sarma.

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.

ß-Cyclodextrin-folate functionalized poly(lactic-co-glycolide)-superparamagnetic ytterbium ferrite hybrid nanocarrier for targeted delivery of camptothecin.

Biocompatible polymer-coated magnetic nanoparticles are designed with an objective to sharp-shoot cancer by loading anticancer drugs on them and delivering to the target site. In this work, novel biocompatible polymers of poly(dl-lactic-co-glycolide), functionalized with ß-cyclodextrin and ß-cyclodextrin-folate conjugate are synthesized and characterized by spectroscopic techniques. Magnetic ytterbium ferrite nanoparticles are prepared, and the synthesized polymers are coated on them. The polymer-coated nanoparticles are intended to be employed as magnetic nanocarriers that transport the anticancer drug, camptothecin. The ferrite nanoparticles are superparamagnetic in nature. Camptothecin was loaded in the nanocarriers and the adsorption percentage was near or above 90%. Study of the in vitro release of camptothecin from the nanocarrier reveals its sustained nature, i.e. a cumulative release of about 50% at 72 h and a pH of 7.4. A pH-dependent enhanced release of 60% is observed, i.e. at a more acidic pH of 6.8. In vitro anti-cancer studies on breast cancer cell lines (MCF7) were carried out. The cell inhibition is enhanced in the case of camptothecin-loaded nanocarrier. The enhanced efficacy of the camptothecin, its sustained release, and the size of the nanocarrier in the range that is considered suitable for magnetic field-assisted drug delivery reveal the magnetic nanocarrier promising for transport of the drug.