ABSTRACT
Cisplatin is a highly effective antitumor drug, which can kill cancer cells by crossing-linking DNA and inhibiting transcription, but this process is limited by the combination of cisplatin and many endogenous nucleophiles, such as glutathione (GSH). Thus, when cisplatin enter cells, it is potentially vulnerable to cytoplasmic inactivation by GSH. To settle this bottleneck, we designed and synthesized a probe compound (Probe 1) and fabricated pH-responsed cisplatin, Probe 1-loaded lipid-polymer hybrid NanoParticles (CPNPs) using a single-step sonication method. Probe 1 can specifically bind to GSH, thus avoiding the combination of GSH and cisplatin, and enhancing the pharmacological activity of cisplatin. In vitro studies have suggested CPNPs, compared with cisplatin, loaded lipid-polymer hybrid NanoParticles CNPs (Not contain Probe 1), could efficiently kill MCF-7 human breast cancer cells and A549 human nonsmall lung cancer cell. Hence, the CPNPs provided a new idea for treating cancer.
Subject(s)
Breast Neoplasms , Cisplatin , Glutathione/metabolism , Lung Neoplasms , Nanoparticles , A549 Cells , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cisplatin/chemistry , Cisplatin/pharmacokinetics , Cisplatin/pharmacology , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/pharmacology , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , MCF-7 Cells , Molecular Probes/chemistry , Molecular Probes/pharmacokinetics , Molecular Probes/pharmacology , Nanoparticles/chemistry , Nanoparticles/therapeutic useABSTRACT
Four new complexes, [Co(dmbpy)2(dca)2]·CH3OH (1), [Ni(dmbpy)2(dca)2]·CH3OH (2), [Zn(dmbpy)2(dca)2]·(3) and [Cu(dmbpy)2(OH)2]·5H2O (4) (dca=dicyanamide), derived from 4,4'-dimethyl-2,2'-bipyridine (dmbpy) have been synthesized and characterized by elemental analysis, TGA and single-crystal X-ray diffraction. Crystal structures and Hirshfeld surfaces analysis revealed that the complexes 1-3 were mainly supported by OHâ¯N, CHâ¯N and πâ¯π intermolecular interactions, and for complex 4, the uncoordinated water molecules play a key role in the construction of the 3D stacking motif. UV spectrum measurements demonstrate that all of the complexes show typical metal to ligand charge transfer (MLCT) absorption bands between 301 and 306nm. Moreover, after complexation, the absorption maximum bands about intraligand πâπ* transitions similarly show slightly red shift compared to dmbpy ligand, consisting with the DFT calculations.
