Targeted drug delivery systems: synthesis and in vitro bioactivity and apoptosis studies of gemcitabine-carbon dot conjugates.

Gemcitabine (GEM) is used to treat various cancers such as breast, pancreatic, non-small lung, ovarian, bladder, and cervical cancers. GEM, however, has the problem of non-selectivity. Water-soluble, fluorescent, and mono-dispersed carbon dots (CDs) were fabricated by ultrasonication of sucrose. The CDs were further conjugated with GEM through amide linkage. The physical and morphological properties of these carbon dot-gemcitabine (CD-GEM) conjugates were determined using different analytical techniques. In vitro cytotoxicity and apoptosis studies of CD-GEM conjugates were evaluated by various bioactivity assays on human cell lines, MCF-7 (human breast adenocarcinoma), and HeLa (cervical cancer) cell lines. The results of kinetic studies have shown a maximum drug loading efficacy of 17.0 mg of GEM per 50.0 mg of CDs. The CDs were found biocompatible, and the CD-GEM conjugates exhibited excellent bioactivity and exerted potent cytotoxicity against tumor cells with an IC50 value of 19.50 µg ml-1 in HeLa cells, which is lower than the IC50 value of pure GEM (∼20.10 µg ml-1). In vitro studies on CD-GEM conjugates demonstrated the potential to replace the conventional administration of GEM. CD-GEM conjugates are more stable, have a higher aqueous solubility, and are more cytotoxic as compared to GEM alone. The CD-GEM conjugates show reduced side effects in the normal cells along with excellent cellular uptake. Hence, CD-GEM conjugates are more selective toward cancerous cell lines as compared to non-cancerous cells. Also, the CD-GEM conjugates successfully induced early and late apoptosis in cancer cell lines and might be effective and safe to use for in vivo applications.

Electrochemical and spectroscopic investigations of carboxylic acid ligand and its triorganotin complexes for their binding with ds.DNA: in vitro biological studies.

A carboxylic acid ligand, (Z)-4-(4-acetylphenylamino)-4-oxobut-2-enoic acid (APA-1), and its triphenyl-(APA-2) and tributyl-tin(IV) (APA-3) compounds have been synthesized and investigated for their binding with ds.DNA using UV-visible spectroscopy, fluorescence spectroscopy, cyclic voltammetry, and viscosity measurements under physiological conditions of pH and temperature. The experimental results from all techniques i.e. binding constant (Kb), binding site size (n) and free energy change (ΔG) were in good agreement and inferred spontaneous compound-DNA complexes formation via intercalation. Among all the compounds APA-3 showed comparatively greater binding at pH 4.7 as evident from its greater Kb values {APA-3: Kb: 5.63×10(4)M(-1) (UV); 7.94×10(4)M(-1) (fluorescence); 9.91×10(4)M(-1) (CV)}. Electrochemical processes of compounds before and after the addition of DNA were found diffusion controlled. Among all compounds, APA-3 exhibited best antitumor activity.

Synthesis, crystal structure, DNA binding and in vitro biological studies of Ni(II), Cu(II) and Zn(II) complexes of N-phthaloylglycine.

Ni(II), Cu(II) and Zn(II) metal complexes of N-phthaloylglycine were synthesized, characterized, reported for single crystal X-ray diffraction analysis for Ni(II) complex, and investigated for their binding with DNA under physiological conditions, using spectroscopic (UV-visible and fluorescence) and hydrodynamic techniques. Experimental results from both spectroscopic methods were comparable and further supported by viscosity measurements. Binding constant "K(b)" obtained from both spectroscopic methods revealed significant binding of compounds with DNA via intercalation. Among all compounds comparatively good DNA binding was found for Zn(II) complex. Free energies of compounds-DNA interactions indicated spontaneity of their binding. Dynamic and bimolecular enhancement values disclose static process involved in compounds-DNA complex formation. All compounds exhibited broad range antibacterial, while Zn(II) complex exhibited best antitumor activity.