Targeted Smart pH and Thermoresponsive N,O-Carboxymethyl Chitosan Conjugated Nanogels for Enhanced Therapeutic Efficacy of Doxorubicin in MCF-7 Breast Cancer Cells.

In cancer treatment, developing ideal anticancer drug delivery systems to target tumor microenvironment by circumventing various physiological barriers still remains a daunting challenge. Here, in our work, a series of pH- and temperature-responsive nanogels based on poly(N-isopropylacrylamide-co-1-propene-2-3-dicarboxylate-co-2-acrylamido-2-methyl-1-propanesulfonate [poly(NIPAAm-IA-AMPS)] cross-linked by ethylene glycol dimethacrylate (EGDMA) were synthesized by random copolymerization. The molar ratio between monomer-comonomers-cross-linker was varied to fine-tune the optimum responsiveness of the nanogels. These optimized nanogels were further coupled to N,O-carboxymethyl chitosan (NOCC) stoichiometrically using EDC-NHS coupling chemistry to enhance the swelling behavior at lower pH. Interestingly, these NOCC-g-nanogels, when dispersed in aqueous media under sonication, attain nanosize and retain their high water-retention capacity with conspicuous pH and temperature responsiveness (viz. nanogel shrinkage in size beyond 35 °C and swelled at acidic pH) in vitro, as reflected by dynamic light scattering data. Doxorubicin (DOX), a potent anticancer drug, was loaded into these nanogels using the physical entrapment method. These drug-loaded nanogels exhibited a slow and sustained DOX release profile at physiological temperature and cytosolic pH. Furthermore, confocal and TEM results demonstrate that these nanogels were swiftly internalized by MCF-7 cells, and cell viability data showed preferential heightened cytotoxicity toward cancer cells (MCF-7 and MDA-MB231) compared to the MCF10A cells (human breast epithelial cell). Furthermore, intracellular DNA damage and cell cycle arrest assays suggest a mitochondrial mediated apoptosis in MCF-7 cells. This study substantiates our NOCC-g-nanogel platform as an excellent modality for passive diffusive loading and targeted release of entrapped drug(s) at physiological conditions in a controlled way for the improved therapeutic efficacy of the drug in anticancer treatment.

Synthesis, spectral and oxidase studies of a new diamide copper(II) complex with pendant benzimidazolyl groups.

A new benzimidazole-based diamide ligand-N,N'-bis(alanine-2-benzimidazolyl) hexanediamide (ABHA) has been synthesized and utilized to prepare Cu(II) complexes of general composition [Cu(ABHA)X2].nH2O,where X is an exogenous anionic ligand (X=Cl-,NO3-). Low temperature EPR spectra has been obtained that shows gparallel>gperpendicular>2.0024, indicating a tetragonal geometry in the solution state. The complexes display a quasi-reversible redox wave due to the Cu(II)/Cu(I) reduction process. E1/2 values shift anodically as NO3-

Copper(II) complexes of N-octylated bis(benzimidazole) diamide ligands and their peroxide-dependent oxidation of aryl alcohols.

New N-octylated benzimidazole-based diamide ligands N,N'-bis(N-octylbenzimidazolyl-2-ethyl)hexanediamide (O-ABHA), possessing a chiral center, and N,N'-bis(N-octylbenzimidazolyl-2-methyl)hexanediamide (O-GBHA) have been synthesized and utilized to prepare Cu(II) complexes of general composition [Cu(L)X]X, where L = O-ABHA or O-GBHA and X = Cl(-) or NO(3)(-) . The X-ray structure of one of the complexes, [Cu(O-GBHA)NO(3)]NO(3), has been obtained. The Cu(II) ion is found to possess a distorted octahedral geometry with a highly unsymmetrical bidentate nitrate group. The N(2)O(2) equatorial plane comprises an amide carbonyl O, a nitrate O, and the two benzimidazole imine N atoms while another amide carbonyl O and nitrate O take up the axial positions. The complexes carry out the oxidation of aromatic alcohols to aldehydes in the presence of cumenyl hydroperoxide at 40-45 degrees C and act as catalyst with turnovers varying between 13- and 27-fold. The percentage yields of the respective products have been obtained which vary from 32% to 65% with respect to the catalyst turnover.