In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4468-4468
Abstract:
Anti-angiogenesis targeted therapy using RNA interference is a powerful tool to inhibit tumor growth and metastasis Here, we developed chitosan/thioaptamer nanoparticles that are capable of cell-type specific binding and delivery of siRNA into tumor-associated endothelial cells Thioaptamer (TA) was created by partial substitution of oxygen with sulfur on the aptamer phosphate backbone at the 5′dA position to enhance binding affinity and stability A combinatorial DNA aptamer library was established for cell-based selection method known as SELEX (systematic evolution of ligands by exponential enrichment) Endothelial cells isolated from both human ovarian tumors and normal human ovarian tissues were used to screen for selective thioaptamers After 10 cycles of cell-SELEX, two candidates, Endo28 and Endo31 showed highly specific binding to both human microvascular endothelial cells (HMVEC) and vasculature of human ovarian cancer tissue Endo28 decorated chitosan nanoparticles (CH/TA-siRNA) were ∼200 nm, positively charged (22mV), and spherical in shape The incorporation of thioaptamer Endo28 and siRNA to chitosan was confirmed using 1HNMR and PCR CH/TA-siRNA nanoparticles were intact and stable in the presence of serum at 37° C Intravenous administration of CH/TA nanoparticles into mice with HeyA8 ovarian tumors resulted in successful binding of aptamer to endothelial cells as well as delivery of siRNA into tumors TEM7 is a tumor biomarker found on the surface of endothelial cells TEM7 silencing using siRNA reduced endothelial tube formation and migration In orthotopic mouse models of ovarian cancer, murine TEM7 siRNA loaded nanoparticles showed substantial reduction in tumor growth as well as reduced angiogenesis These data have implications for new anti-angiogenesis approaches Citation Format: Dahai Jiang, Lingegowda S. Mangala, Hongyu Wang, Sherry Wu, Lokesh G. Rao, Cristian Rodriguez-Aguayo, Sunila Pradeep, David E. Volk, Gabriel Lopez-Berestein, Anil K. Sood. Tumor vasculature targeting using cell-specific thioaptamer decorated chitosan nanoparticle. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4468. doi:10.1158/1538-7445.AM2014-4468
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-4468
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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