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DNA nanotherapy for pre-neoplastic cervical lesions.
Peng, Weidan; Dunton, Charles; Holtz, David; Parva, Mehdi; Stampler, Kate; Forwood, Mark; Gogoi, Radhika; Lace, Michael J; Anderson, Daniel G; Sawicki, Janet A.
Afiliación
  • Peng W; Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: pengw@mlhs.org.
  • Dunton C; Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA; Lankenau Medical Center, 100 Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: duntonc@mlhs.org.
  • Holtz D; Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA; Lankenau Medical Center, 100 Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: holtzd@mlhs.org.
  • Parva M; Lankenau Medical Center, 100 Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: mmparva@gmail.com.
  • Stampler K; Lankenau Medical Center, 100 Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: stamplerk@mlhs.org.
  • Forwood M; Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: mff204@gmail.com.
  • Gogoi R; Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA; Lankenau Medical Center, 100 Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: rpgogoi@geisinger.com.
  • Lace MJ; Veterans Affairs Medical Center, 601 Highway 6 west, Iowa City, IA 52242, USA; Carver College of Medicine, University of Iowa, 451 Newton Rd., 200 Medicine Admst. Bldg., Iowa City, IA 52242, USA. Electronic address: Michael-lace@uiowa.edu.
  • Anderson DG; Massachusetts Institute of Technology, 77 Massachusetts Ave., Bldg. 76, Rm. 653, Cambridge, MA 02142, USA. Electronic address: dgander@mit.edu.
  • Sawicki JA; Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA; Thomas Jefferson University, Kimmel Cancer Center, 925 Chestnut St., Philadelphia, PA 19107, USA. Electronic address: sawickij@mlhs.org.
Gynecol Oncol ; 128(1): 101-106, 2013 Jan.
Article en En | MEDLINE | ID: mdl-23103931
OBJECTIVE: This study aims to test the hypothesis that targeted nanoparticle delivery of DNA encoding HPV16-regulated diphtheria toxin (DT-A) will result in the death of HPV16-infected cells. MATERIALS AND METHODS: Plasmid constructs containing a HPV16 Long Control Region (LCR) DNA sequence upstream of DT-A or luciferase reporter (Luc) DNA sequences were used to formulate poly(ß-amino ester) nanoparticles. The effect on tumor growth of HPV/DT-A-nanoparticle injection directly into HPV16(+) CaSki human cervical cancer cell-derived xenografts in mice was determined. To evaluate the ability of the HPV16 LCR regulatory sequence to activate gene expression specifically in HPV16-infected cells, mice underwent bioluminescent optical imaging following intraperitoneal injection of HPV/Luc-nanoparticles. The use of Lutrol F127, a thermal-sensitive gel, to target delivery of nanoparticles and subsequent gene expression to cervical epithelial cells was evaluated in ex vivo cultures of mouse cervix and following intravaginal delivery of nanoparticle/gel in mice, as well as in ex vivo cultures of surgical LEEP samples. RESULTS: The selected HPV16 LCR regulatory sequence activates gene expression in both HPV16-infected cells and non-infected cells. However, in the cervix, it is specifically active in epithelial cells. Following exposure of cervical cells to HPV/DT-A-nanoparticles mixed with Lutrol F127 gel, DT-A is expressed and cells die. CONCLUSIONS: An HPV16 DNA sequence that targets gene expression specifically to HPV16-infected cells remains to be discovered. Topical application of a Lutrol F127 thermal gel/nanoparticle mix is illustrative of how to restrict exposure of cells to therapeutic nanoparticles, thereby allowing for targeted DNA delivery to cervical pre-cancerous lesions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Lesiones Precancerosas / ADN / Neoplasias del Cuello Uterino / Toxina Diftérica / Papillomavirus Humano 16 / Nanopartículas Límite: Animals / Female / Humans Idioma: En Revista: Gynecol Oncol Año: 2013 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fragmentos de Péptidos / Lesiones Precancerosas / ADN / Neoplasias del Cuello Uterino / Toxina Diftérica / Papillomavirus Humano 16 / Nanopartículas Límite: Animals / Female / Humans Idioma: En Revista: Gynecol Oncol Año: 2013 Tipo del documento: Article Pais de publicación: Estados Unidos