Ectopic high endothelial venules in pancreatic ductal adenocarcinoma: A unique site for targeted delivery
MetadataShow full item record
AbstractBackground: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79. Methods: Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC. Findings: The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was more robust than non-conjugated NPs. Treatment with MECA79-Taxol-NPs augmented the delivery of Paclitaxel (Taxol) to the tumor site and significantly reduced the tumor size. This effect was associated with a higher apoptosis rate of PDAC cells and reduced vascularization within the tumor. Interpretation: Targeting the HEVs of PDAC using MECA79-NPs could lay the ground for the localized delivery of a wide variety of drugs including chemotherapeutic agents. Copyright 2018 The Authors
SponsorsThis work is in part supported by the following National Institutes of Health (NIH) grants: T32-EB016652 (B.B.), NIH Cancer Core Grant CA034194 (L.D.S.), National Institute of Allergy and Infectious Diseases grants R01-AI126596 and R01-HL141815 (R.A.)
KeywordHigh endothelial venules
MECA79 coated nanoparticles
Pancreatic ductal adenocarcinoma
Peripheral node addressin
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85057125177&doi=10.1016%2fj.ebiom.2018.11.030&partnerID=40&md5=079996ec9b584bd3e92382d279929bfc; http://hdl.handle.net/10713/9645
- Treatment of pancreatic ductal adenocarcinoma with tumor antigen specific-targeted delivery of paclitaxel loaded PLGA nanoparticles.
- Authors: Wu ST, Fowler AJ, Garmon CB, Fessler AB, Ogle JD, Grover KR, Allen BC, Williams CD, Zhou R, Yazdanifar M, Ogle CA, Mukherjee P
- Issue date: 2018 Apr 23
- Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival.
- Authors: Bahmani B, Uehara M, Jiang L, Ordikhani F, Banouni N, Ichimura T, Solhjou Z, Furtmüller GJ, Brandacher G, Alvarez D, von Andrian UH, Uchimura K, Xu Q, Vohra I, Yilmam OA, Haik Y, Azzi J, Kasinath V, Bromberg JS, McGrath MM, Abdi R
- Issue date: 2018 Nov 1
- Interleukin 35 Expression Correlates With Microvessel Density in Pancreatic Ductal Adenocarcinoma, Recruits Monocytes, and Promotes Growth and Angiogenesis of Xenograft Tumors in Mice.
- Authors: Huang C, Li Z, Li N, Li Y, Chang A, Zhao T, Wang X, Wang H, Gao S, Yang S, Hao J, Ren H
- Issue date: 2018 Feb
- A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma.
- Authors: Indolfi L, Ligorio M, Ting DT, Xega K, Tzafriri AR, Bersani F, Aceto N, Thapar V, Fuchs BC, Deshpande V, Baker AB, Ferrone CR, Haber DA, Langer R, Clark JW, Edelman ER
- Issue date: 2016 Jul
- The anti-fibrotic effect of GV1001 combined with gemcitabine on treatment of pancreatic ductal adenocarcinoma.
- Authors: Park JK, Kim Y, Kim H, Jeon J, Kim TW, Park JH, Hwnag YI, Lee WJ, Kang JS
- Issue date: 2016 Nov 15