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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
MTX inhibits the action of the FA reductase, which is responsible for conversion of FA to tetrahydrofolic acid [362, 363]. In the absence of tetrahydrofolic acids, DNA, RNA, and proteins cannot be synthesized, leading to blockage of cell division. Hydroxyurea (hyhdroxycarbamide) reduces production of deoxyribonucleotides through inhibition of the enzyme ribonucleotidereductase [361–366]. This enzyme catalyzes the reduction of ribonucleotide into their corresponding deoxyribonucleotides, which are required for DNA synthesis. 5-FU, a thymidylate synthase inhibitor, is widely used in the treatment of patients with breast or gastrointestinal tract cancer. Interrupting the action of this enzyme blocks the synthesis of pyrimidine thymidine, which is a nucleoside required for DNA replication, in the S phase of the cell cycle [367]. Thymidylate synthase converts deoxyuridine monophosphate (dUMP) into deoxythymidine monophosphate (dTMP), which is crucial in production of pyrimidine base for synthesis of DNA; thus, it is a viable target for cancer chemotherapy [367]. 5-FU causes a scarcity of dTMP. Therefore, rapidly dividing cancer cells undergo apoptosis via thymine-less death. 5-FU can arrest unlimited proliferation of cancer cells and also lead to production of faulty rRNA [368, 369]. The immunosuppressive drug 6-MP alters the synthesis and function of DNA and RNA by inhibiting purine nucleotide synthesis and metabolism and interferes with nucleotide interconversion and glycoprotein synthesis [370, 371].
Plasmonic photothermal effect on cytotoxicity of biogenic nanostructure synthesized through Litchi chinensis Sonn.
Published in Inorganic and Nano-Metal Chemistry, 2021
It is shown from earlier research that less amount of Se can get rid of reactive oxygen species (ROS) and the repairing of damaged DNA by seleno-enzymes that results in cell protection. High concentration of ROS contributes to cell apoptosis and cancer cells get destroyed. Se acts as the new therapeutic agent for the treatment of cancer. Zero valent Selenium (Se) NPs contain a formulation of high Se density that has the potential to deliver high doses to tumor cells locally relative to other types of selenium.[14] Silver (Ag) nanoparticles have drawn significant scientific interest due to the fact that their application, such as medical imaging, delivery of drugs and antimicrobial agents. Ag is viewed as tremendous antitumor agent due to its antiproliferative and apoptosis inducing properties.[15,16] A broad spectrum anticancer drug 5-Fluorouracil (5-FU) is a pyrimidine analog used in the treatment of breast cancer and various malignancies. 5-FU interferes with DNA synthesis and acts as thymidylate synthase inhibitor. However, the clinical use of 5-FU results in significant limitations such as rapid metabolism, nonselective biodistribution, and its adverse aspects.[17,18] Evidence strongly suggests that the efficacy of 5-FU as a chemo drug in the treatment of cancer may be enhanced by a combinational approach using traditional chemo drugs or even other nontoxic plant-derived components such as genistein and curcumin.[19]
A microporous Co(II)-MOF as a pH-responsive 5-Fu delivery system to induce human hemangioma cells apoptosis and abrogate their growth
Published in Journal of Coordination Chemistry, 2020
Qi-Qi Wang, Zhi-Peng Yang, Zhong-Tao Cui, Xiao-Hui Wang, Yao Lin
A route using porous MOFs has been proposed to replace previously unsuccessful systems of drug delivery. These materials provide some advantages, for example, highly adjustable structures, achieved by changing metal or/and organic connectors to effectively adjust chemical performance, structure and pore size [7–12]. These solids possess high pore volumes (the proportion of pore volume to the total volume), active binding sites in the skeleton and regular porosity, which makes it easy to use guest molecules and provides opportunities for their applications in medical and biomedical fields. 5-Fluorouracil (5-Fu), a pyrimidine analog, is a broad spectrum anticancer drug used in the treatment of malignancies like glioblastoma and breast cancer [13–15]. Since 5-Fu interferes with DNA synthesis, it principally acts as a thymidylate synthase inhibitor. However, short half-life, wide distribution, and various side effects limit its medical applicability. To overcome the above-mentioned limitations, studies have been carried out on sustained drug delivery systems for 5-fluorouracil [16–18]. Due to its small molecular size as well as abundant H-bond donor and acceptor sites, it is an ideal molecule to be loaded into the pores of MOFs to achieve the drug delivery system. Zhou and co-workers prepared a porous MOF consisting of a nanocage, Cu(pi)-PEG5k, with a 5-Fu loading capacity of 4.38% [19]. It is more significant to construct intrinsic smart MOFs based on the stimuli-responsiveness of organic ligands or on the coordination between the ligand and the metal, such as MOFs with pH-dependent stabilities [20–22]. For instance, Zou et al. reported the one-pot synthesis of anticancer drugs loaded into ZIF-8 nanocarriers based on the pH-sensitivity of ZIF-8 toward the acidic microenvironment at tumor sites [23]. In this work, a microporous metal-organic framework containing Co(II) which has a polar pore surface has been prepared under solvothermal conditions. Complex 1 was characterized via single crystal X-ray diffraction, powder X-ray diffraction (PXRD), thermogravimetric analysis and experiments of N2 sorption at 77 K. The diamond-shaped channels of the framework for 1 are 6.1 Å along the b axis of the crystal, and the surface area of BET is 541 m2·g−1. FT-IR spectra demonstrated 5-Fu loading and ultraviolet–visible spectra showed the loading capacity of 5-Fu is 27.36%. Compared with normal tissue of pH = 7.4, the drug release in simulated cancer tissue of pH = 5.7 showed gradual rational pH-responsive drug release. Using colony formation test and CCK-8, 5-Fu@1a was tested for its antitumor and proliferative activity against EOMA hemangioma cells, and it was predicted that 5-Fu@1a has good antitumor effect in vitro. In order to study the tumor cell death, Western blot and apoptosis were detected. The results showed that 5-Fu@1a could induce caspase dependent EOMA cells death. The significant inhibitory effect for 5-Fu@1a in mice has been further demonstrated through the results of body weight and tumor volume in vivo.