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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
Drugs such as cisplatin, the antibiotics daunorubicin and DOX, and etoposide disrupt the replication of the DNA and cause formation of nonsense DNA or RNA by inhibiting telomerase activity or eliminating telomeric DNA. Telomerase as the natural enzyme for elongating telomeres enables cancer cells to divide virtually forever. Immortalization of cancer cells is considered to stem from their activity [354, 360]. Therefore, DOX, which is effective in treatments of acute leukemia, malignant lymphoma, and a variety of solid tumors, acts by intercalating between nucleic acid bases. It also inhibits the action of the enzyme topoisomerase II, thereby interfering with DNA and RNA biosynthesis. The four planar rings of the drug intercalate into DNA, whereas the hydroxyl group on the side chain interacts with topoisomerases II, which causes cleavage of DNA to stop the replication process [372, 373]. However, because it induces common toxicities, including cardiotoxicity [38], attempts to reduce its toxicity have been made by introducing novel carrier systems such as PEGylated liposomes [374–380]. Etoposide does not intercalate into DNA but forms a ternary complex with DNA and topoisomerase II enzyme, thereby preventing religation of the DNA strands, inducing errors in DNA synthesis and apoptosis of cancer cells [372–373].
PLGA-Based Nanoparticles for Cancer Therapy
Published in Jince Thomas, Sabu Thomas, Nandakumar Kalarikkal, Jiya Jose, Nanoparticles in Polymer Systems for Biomedical Applications, 2019
Etoposide is an anticancer agent used in the treatment of a variety of malignancies, including malignant lymphomas. It acts by inhibition of topoisomerase-II and activation of oxidation–reduction reactions to create derivatives that bind directly to DNA and cause DNA damage. The successful chemotherapy of tumors depends on continual exposure to anticancer agents for long-lasting periods. Etoposide has a short biological half-life (3.6 h), and although intraperitoneal injection would cause initial high local tumor concentrations, long-lasting exposure of tumor cells may not be probable. It is envisaged that intraperitoneal delivery of etoposide through NPs would be a better approach for effectual treatment of peritoneal tumors. In this perception, etoposide-loaded NPs were prepared applying nanoprecipitation and emulsion-solvent evaporation methods using PLGA in the presence of Pluronic F68 by Reddy et al. The process produced NPs with high entrapment efficiency of around 80% with continuous release of the drug up to 48 h.89
Solid Lipid Nanoparticles for Anti-Tumor Drug Delivery
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Ho Lun Wong, Yongqiang Li, Reina Bendayan, Mike Andrew Rauth, Xiao Yu Wu
Etoposide, all-trans retinoic acid (ATRA), and butyric acid are all lipophilic molecules that have anti-tumor properties. Out of these three compounds, etoposide (Vepesid, VP-16) has the longest history in cancer chemotherapy and is still in clinical use for the treatment of several forms of cancer. Etoposide is a plant alkaloid. It inhibits topoisomerase II and produces reactive derivatives that can lead to DNA strand break.102 This drug was successfully encapsulated in SLN made of tripalmitin.80 The authors quoted that the particles were stable after four months of preparation with excellent redispersibility. However, probably because the focus of that study was on the evaluation of drug biodistribution and in vivo anti-tumor efficacy, few details in this area was revealed. The SLN system demonstrated an excellent encapsulation efficiency of 98.96% with 4% payload of etoposide obtained.
Usnic acid attenuates genomic instability in Chinese hamster ovary (CHO) cells as well as chemical-induced preneoplastic lesions in rat colon
Published in Journal of Toxicology and Environmental Health, Part A, 2019
Nayane Moreira Machado, Arthur Barcelos Ribeiro, Heloiza Diniz Nicolella, Saulo Duarte Ozelin, Lucas Henrique Domingos Da Silva, Ana Paula Prado Guissone, Francisco Rinaldi-Neto, Igor Lizo Limonti Lemos, Ricardo Andrade Furtado, Wilson Roberto Cunha, Alexandre Azenha Alves De Rezende, Mário Antônio Spanó, Denise Crispim Tavares
In an attempt to contribute to the understanding of MOA underlying the antigenotoxic effect previously reported by Leandro et al. (2013), the influence of UA was investigated on genotoxicity induced by mutagens with differing MOA such as DXR, H2O2, and VP-16. DXR, an anthracycline antibiotic, is a key chemotherapeutic drug employed for cancer treatment, although its use is limited by chronic and acute adverse effects (Quiles et al. 2002). Anthracyclines such as DXR are DNA topoisomerase II inhibitors. This enzyme is involved in fundamental biological processes, including DNA replication, transcription, DNA repair, and chromatin remodeling. DXR binds to DNA topoisomerase II and stabilizes an intermediate reaction in which the DNA strands are cut and covalently linked to tyrosine residues of DNA topoisomerase II, creating a ternary DXR–DNA–DNA topoisomerase II complex that alters DNA structure and impedes its synthesis (Minotti et al. 2004). Further, the quinone present in the molecular structure of DXR may be oxidized to a semiquinone radical. Semiquinone radicals react rapidly with oxygen to generate superoxide (O2−) and H2O2 that are converted to highly reactive hydroxyl radicals, inducing DNA damage (Finn, Findley, and Kemp 2011; Injac and Strukelj 2008; Venkatesh et al. 2007).
Nuclear targeting peptide-modified, DOX-loaded, PHBV nanoparticles enhance drug efficacy by targeting to Saos-2 cell nuclear membranes
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Ayla Şahin, Gozde Eke, Arda Buyuksungur, Nesrin Hasirci, Vasif Hasirci
Another observation with CLSM is the cell membrane of the cytoplasm of Saos-2 cells (Figure 4(E) and (F)) indicating that DOX molecules were effectively delivered into the nucleus. The main action of DOX on cancer cells is based on inhibition of Topoisomerase II which causes the generation of free radicals. These free radicals damage proteins, DNA and the membranes inducing apoptosis through cleavage of DNA and formation of hydrogen peroxide [21,28]. According to the literature, since the cells cannot go through replication due to the intercalation of DNA by DOX, they may go through apoptosis or necrosis since the cell membrane is disrupted. Thus, the targeted nanoparticles carried their DOX cargo to the nuclear membrane, the DOX was released there and penetrated the nucleus and showed its apoptotic effect.
Fabricating of Fe3O4@Ag-MOF nanocomposite and evaluating its adsorption activity for removal of doxorubicin
Published in Journal of Environmental Science and Health, Part A, 2022
N. M. El-Metwaly, H. A. Katouah, M. G. El-Desouky, A. A. El-Bindary, M. A. El-Bindary
Doxorubicin is an anthracycline antibiotic with anti-cancer activity. Doxorubicin was produced by the bacteria Streptomyces peucetius var. and is the hydroxylated congener of daunorubicin. caesius. Doxorubicin suppresses protein synthesis to stop DNA replication, the DNA helix is intercalated between base pairs. Doxorubicin also inhibits topoisomerase II, enhancing the consistency of the enzyme-DNA complex during DNA replication and avoiding the ligation of the nucleotide strand following double-strand breaks. Doxorubicin also generates oxygen free radicals, which result in cytotoxicity because they peroxide the lipids in cell membranes. The impact of oxygen free radicals on the heart and blood arteries make the anthracycline antibiotics particularly dangerous.