Redox Proteomic Profile of Tirapazamine-Resistant Murine Hepatoma Cells.

3-Amino-1,2,4-benzotriazine-1,4-dioxide (tirapazamine, TPZ) and other heteroaromatic -oxides (ArN→O) exhibit tumoricidal, antibacterial, and antiprotozoal activities. Their action is attributed to the enzymatic single-electron reduction to free radicals that initiate the prooxidant processes. In order to clarify the mechanisms of aerobic mammalian cytotoxicity of ArN→O, we derived a TPZ-resistant subline of murine hepatoma MH22a cells (resistance index, 5.

Uptake of Upconverting Nanoparticles by Breast Cancer Cells: Surface Coating versus the Protein Corona.

Fluorophores with multifunctional properties known as rare-earth-doped nanoparticles (RENPs) are promising candidates for bioimaging, therapy, and drug delivery. When applied , these nanoparticles (NPs) have to retain long blood-circulation time, bypass elimination by phagocytic cells, and successfully arrive at the target area. Usually, NPs in a biological medium are exposed to proteins, which form the so-called "protein corona" (PC) around the NPs and influence their targeted delivery and accumulation in cells and tissues.

Proteomic Analysis of Breast Cancer Resistance to the Anticancer Drug RH1 Reveals the Importance of Cancer Stem Cells.

Antitumor drug resistance remains a major challenge in cancer chemotherapy. Here we investigated the mechanism of acquired resistance to a novel anticancer agent RH1 designed to be activated in cancer cells by the NQO1 enzyme. Data show that in some cancer cells RH1 may act in an NQO1-independent way.

Molecular modeling and structure-based drug discovery approach reveals protein kinases as off-targets for novel anticancer drug RH1.

Potential drug target identification and mechanism of action is an important step in drug discovery process, which can be achieved by biochemical methods, genetic interactions or computational conjectures. Sometimes more than one approach is implemented to mine out the potential drug target and characterize the on-target or off-target effects. A novel anticancer agent RH1 is designed as pro-drug to be activated by NQO1, an enzyme overexpressed in many types of tumors.

Tailored Dual PEGylation of Inorganic Porous Nanocarriers for Extremely Long Blood Circulation in Vivo.

Drug carrier systems based on mesoporous inorganic nanoparticles generally face the problem of fast clearance from bloodstream thus failing in passive and active targeting to cancer tissue. To address this problem, a specific dual PEGylation (DPEG) method for mesoporous silicon (PSi) was developed and studied in vitro and in vivo. The DPEG coating changed significantly the behavior of the nanoparticles in vivo, increasing the circulation half-life from 1 to 241 min.

Surface properties of quantum dots define their cellular endocytic routes, mitogenic stimulation and suppression of cell migration.

The practical use of quantum dots (QD) as diagnostic, visualizing and therapeutic nano-agents depends on the understanding of fundamental mechanisms of their entrance and trafficking within cells. Here we show that CdSe/ZnS carboxylic-coated QD (COOH-QD) enter fibroblast cells via lipid raft/caveolin-mediated endocytosis, pass early sorting endosomes and accumulate in the multivesicular bodies, but not in the lysosomes. Later phase of their endocytosis leads to the generation of lipid raft/caveolin-dependent endocytosis inhibition that prevents intracellular uptake of new COOH-QD, but not the QD coupled with platelet-derived growth factor BB (PDGF-QD).