Abstract 1965: Evaluating the use of Fe3O4@TiO2 nanoparticles and nanoconjugates with a HPV 18 E2 peptide as a potential therapy for HPV containing cancer cells
| Autor: | Aiguo Wu, Gayle E. Woloschak, Ye Yuan, Caroline Doty, Tatjana Paunesku |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Cancer Research. 72:1965-1965 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2012-1965 |
| Popis: | Over half a million women world wide are affected by cervical cancer each year. HPV, human papillomavirus, is currently seen as the causative agent of this form of cancer. There are multiple mechanisms by which HPV can cause cervical cancer, the primary mechanisms being the integration of HPV viral DNA into human DNA and the production of the viral oncoproteins E6 and E7. The mechanism of action of these oncoproteins lies in the deregulation of tumor suppressor proteins p53 and Rb. Current cervical cancer therapies, such as radiation, surgical removal, and chemotherapy target the cancerous cells but not the causative agent, HPV. The purpose of this investigation is to find the optimal formulation for, and evaluate the ability of, titanium dioxide (TiO2) shell - iron oxide (Fe3O4) core nanoconjugates (Fe3O4@TiO2) to target HPV genome as a method of therapy. Fe3O4@TiO2, which act the same as pure TiO2 nanoparticles, produce reactive oxygen species (ROS) in solution and have the ability to cleave DNA upon the induction of photon energies above 3.2 eV (e.g. white light), as was shown as a part of these studies. In this study, 6nm Fe3O4@TiO2 nanoconjugates were covalently linked, via a dopamine linker, to a truncated HPV 18 E2 peptide. The peptide linked to the nanoparticle is a 22 amino acid sequence that contains a nuclear localization sequence as well as a DNA binding motif. We hypothesized that (1) the Fe3O4@TiO2-PNA nanoconjugates would localize to the nucleus of cells; (2) presence of nanoconjugates in cells would lead to the production of reactive oxygen species (ROS) upon induction with white light; (3) presence of light activated nanoconjugates in cells would lead to double strand breaks in DNA. The nanoconjugate was tested in HeLa cells which contain multiple copies of HPV genome. To evaluate the effectiveness of this nanoconjugate therapy, we have used DCFDA staining to determine levels of ROS in cells upon the induction of light. As a method to determine double strand DNA damage, we have used immunofluorescence techniques to reveal changes in 53BP1 foci. Upon the introduction and induction of Fe3O4@TiO2-HPV 18 E2 peptide nanoconjugates in HeLa cells we have found increases in ROS levels and increases 53BP1 foci suggesting the presence of double strand DNA damage. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1965. doi:1538-7445.AM2012-1965 |
| Databáze: | OpenAIRE |
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