| Literature DB >> 27777972 |
Lingegowda S Mangala1,2, Hongyu Wang3,4, Dahai Jiang1,2, Sherry Y Wu1, Anoma Somasunderam5, David E Volk3,4, Ganesh L R Lokesh3, Xin Li3, Sunila Pradeep1, Xianbin Yang6, Monika Haemmerle1, Cristian Rodriguez-Aguayo2,7, Archana S Nagaraja1, Rajesha Rupaimoole1, Emine Bayraktar7, Recep Bayraktar7, Li Li3, Takemi Tanaka8, Wei Hu1, Cristina Ivan1, Kshipra M Gharpure1, Michael H McGuire1, Varatharasa Thiviyanathan3,4, Xinna Zhang1,2, Sourindra N Maiti9, Nataliya Bulayeva3, Hyun-Jin Choi1, Piotr L Dorniak1, Laurence Jn Cooper9, Kevin P Rosenblatt10, Gabriel Lopez-Berestein2,7,11, David G Gorenstein3,4,6, Anil K Sood1,2,11.
Abstract
Current antiangiogenesis therapy relies on inhibiting newly developed immature tumor blood vessels and starving tumor cells. This strategy has shown transient and modest efficacy. Here, we report a better approach to target cancer-associated endothelial cells (ECs), reverse permeability and leakiness of tumor blood vessels, and improve delivery of chemotherapeutic agents to the tumor. First, we identified deregulated microRNAs (miRs) from patient-derived cancer-associated ECs. Silencing these miRs led to decreased vascular permeability and increased maturation of blood vessels. Next, we screened a thioaptamer (TA) library to identify TAs selective for tumor-associated ECs. An annexin A2-targeted TA was identified and used for delivery of miR106b-5p and miR30c-5p inhibitors, resulting in vascular maturation and antitumor effects without inducing hypoxia. These findings could have implications for improving vascular-targeted therapy.Entities:
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Year: 2016 PMID： 27777972 PMCID： PMC5070952 DOI： 10.1172/jci.insight.87754
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708