Improving the Anticancer Efficacy of Laminin Receptor-Specific Therapeutic Ruthenium Nanoparticles (RuBB-Loaded EGCG-RuNPs) via ROS-Dependent Apoptosis in SMMC-7721 Cells.

Functionalization can promote the uptake of nanoparticles into cancer cells via receptor-mediated endocytosis, enabling them to exert their therapeutic effects. In this paper, epigallocatechin gallate (EGCG), which has a high binding affinity to 67 kDa laminin receptor (67LR) overexpressed in HCC cells, was employed in the present study to functionalized ruthenium nanoparticles (RuNPs) loaded with luminescent ruthenium complexes to achieve antiliver cancer efficacy. [Ru(bpy)2(4-B)] (ClO4)2·2H2O (RuBB)-loaded EGCG-RuNPs (bpy = 2,2'-bipyridine) showed small particle size with narrow distribution, better stability, and high selectivity between liver cancer and normal cells. The internalization of RuBB-loaded EGCG-RuNPs was inhibited by 67LR-blocking antibody or laminin, suggesting that 67LR-mediated endocytosis played an important role in the uptake into HCC cells. Moreover, transmission electron microscopy and confocal microscopic images showed that RuBB-loaded EGCG-RuNPs accumulated in the cytoplasm of SMMC-7721 cells. Furthermore, our results indicated that the EGCG-functionalized nanoparticles displayed enhanced anticancer effects in a target-specific manner. Concentrations of RuBB-loaded EGCG-RuNPs, nontoxic in normal L-02 cells, showed direct reactive oxygen species-dependent cytotoxic, pro-apoptotic, and anti-invasive effects in SMMC-7721 cells. Furthermore, in vivo animal study demonstrated that RuBB-loaded EGCG-RuNPs possessed high antitumor efficacy on tumor-bearing nude mice. It is encouraging to conclude that the multifunctional RuNPs may form the basis of new strategies on the treatment of liver cancer and other malignancies.

Multifunctional selenium nanoparticles: Chiral selectivity of delivering MDR-siRNA for reversal of multidrug resistance and real-time biofluorescence imaging.

Herein, chiral selenium nanoparticles (L-SeNPs/D-SeNPs) modified with a dinuclear Ruthenium (II) complex were used to effectively deliver siRNA targeting the MDR1 gene. In this co-delivery system, the luminescent dinuclear Ruthenium (II) complex was developed to act as a gene carrier and anti-tumor drug, while offering luminescent imaging to follow the intracellular trafficking. Interestingly, Ru@L-SeNPs exhibited a stronger protein and pDNA affinity than Ru@D-SeNPs, indicating that chirality may have an effect on pDNA/siRNA binding and biocompatibility. Cisplatin-resistant A549R cells treated with Ru@L-SeNPs-siRNA demonstrated significant downregulation of P-glycoprotein (P-gp) expression, resulting in unprecedented enhanced cytotoxicity through the induction of apoptosis with the involvement of phosphorylation of p53, MAPK and PI3K/Akt signaling pathways. In vivo investigation confirmed that Ru@L-SeNPs-siRNA nanoparticles exhibited high tumor-targeted fluorescence, enhanced anti-tumor efficacy, and decreased systemic toxicity. These results suggest that Ru@L-SeNPs are promising vectors for the delivery of siRNA and for real-time tracking of treatment. FROM THE CLINICAL EDITOR: In this study, the authors designed bi-functional selenium nanoparticles with specific chirality to deliver siRNA, for targeting tumor MDR1 gene. The underlying ruthenium (II) complex could also offer fluorescence for real-time imaging. This new system has been shown to have enhanced efficacy against drug resistant tumor cells in both in-vitro and in-vivo experiments.

Synthesis and 3D-QSAR study of 1,4-dihydropyridine derivatives as MDR cancer reverters.

A series of symmetrical and unsymmetrical 1,4-dihydropyridines were synthesized by a rapid, single pot microwave irradiation (MWI) based protocol along with conventional approach and characterized by NMR, IR and mass spectroscopic techniques. The compounds were evaluated for their tumor cell cytotoxicity in HL-60 tumor cells. A 3D-QSAR study using CoMFA and CoMSIA was carried out to decipher the factors governing MDR reversing ability in cancer. The resulting contour maps derived by the best 3D-QSAR models provide a good insight into the molecular features relevant to the biological activity in this series of analogs. 3D contour maps as a result of 3D-QSAR were utilized to identify some novel features that can be incorporated into the 1,4-dihydropyridine framework to enhance the activity.

Synthesis and in vitro anti-HIV activity of N-1,3-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT method.

A series of novel N-1,3-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives has been synthesized. All the newly synthesized compounds were evaluated for their anti-HIV activity using MTT method. Most of these compounds showed moderate to potent activity against wild-type HIV-1 with an EC(50) ranging from >7 EC(50) [µg/ml] to <100 EC(50) [µg/ml]. Among them, N-1,3-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide 6v was identified as the most promising compound (EC(50)=<7 µg/ml). Among all the compounds, three compounds 6m, 6v and 6u have been exhibits potent anti-HIV activity against MT-4 cells.

Synthesis of some novel benzofuran-2-yl(4,5-dihyro-3,5-substituted diphenylpyrazol-1-yl) methanones and studies on the antiproliferative effects and reversal of multidrug resistance of human MDR1-gene transfected mouse lymphoma cells in vitro.

A new series of benzofuran-2-yl(4,5-diydro-3,5-substituted diphenylpyrazol-1-yl) methanone derivatives 8a-x by the reaction of the benzofuran-2-carbohydrazides 7 with various chalcone derivatives 3a-x using microwave irradiation has been described. The effect of synthesized compounds 8a-v was studied against human cancer cell lines for their antiproliferative activity and reversal of multidrug resistance on human MDR1-gene transfected mouse lymphoma cells. Among the 24 compounds, the 8c and 8h showed good antiproliferative activity 8b, 8f and 8k were exhibited good MDR reversal activity. The main significance of the process is easy workup process, short reaction time and high yield of the new compounds for biological interest. However, the studies on genetically modified multidrug resistant cancer cells are costly and time consuming.

Synthesis and biological evaluation of 4-styrylcoumarin derivatives as inhibitors of TNF-α and IL-6 with anti-tubercular activity.

A series of 4-styrylcoumarin have been synthesized by Knoevenagel condensation between substituted 4-methylcoumarin-3-carbonitrile and different heterocyclic or aromatic aldehydes. 4-Methylcoumarin-3-carbonitrile has been synthesized by the base catalyzed reaction between substituted 2-hydroxyacetophenone and ethyl cyanoacetate. The structures of the newly synthesized compounds were confirmed by (1)H NMR, IR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory activity (against TNF-α and IL-6) and anti-tubercular activity. Compounds 6a, 6h and 6j exhibited promising activity against IL-6 with 72-87% inhibition and compound 6v showed potent activity against TNF-α with 73% inhibition at 10 µM concentration. Whereas compounds 6n, 6o, 6r and 6u showed very good anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at <6.25 µM.