Thursday, November 29, 2018

Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used in development of nanoparticle pancreatic-cancer therapy

Pancreatic ductal adenocarcinoma (PDA) is a difficult to treat and typically fatal form of pancreatic cancer. Part of the difficulty in treatment is the relatively low vascularization in the tumor region for this type of cancer which prevents uptake of medicinal therapies. Use of nanoparticles decorated with a targeting ligand could improve drug delivery to this region. Recently, researchers at Harvard Medical School used mPEG-PLGA (AK102) and mal-PEG-PLGA (AI110) from PolySciTech (www.polyscitech.comto develop nanoparticles covered with MECA79 targeting antibody and investigated their transport and uptake. This research holds promise for improved therapies against this fatal disease. Read more: Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K. Eskandari, Nasim Annabi, Jonathan S. Bromberg, Leonard D. Shultz, Dale L. Greiner, Reza Abdi “Ectopic high endothelial venules in pancreatic ductal adenocarcinoma: A unique site for targeted delivery” EBioMedicine (2018) Read more: https://www.ebiomedicine.com/article/S2352-3964(18)30534-6/fulltext

“Background: 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.”

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