Glioma-targeted therapy using Cilengitide nanoparticles combined with UTMD enhanced delivery

Journal of Controlled Release : Official Journal of the Controlled Release Society
Ying-Zheng ZhaoCui-Tao Lu

Abstract

Malignant gliomas especially glioblastoma (GBM) are poorly responsive to the current treatments. Cilengitide (CGT) is a cyclic pentapeptide that demonstrated efficacy for GBM treatment by targeting the integrins avβ3 and avβ5 over-expressed on GBM cells. However, clinical translation of this therapy has been limited by issues including fast blood clearance, high kidney and liver uptake, poor blood-brain barrier (BBB) penetration, low tumor specificity and rapid washout from tumors. In this study, these issues were tackled in an integrated manner using a multi-stage strategy combining ultrasound-targeted microbubble destruction (UTMD) with CGT nanotherapy. CGT nanoparticles (CGT-NP) prepared using gelatin and Poloxamer 188-grafted heparin copolymer demonstrated significant apoptotic and cytotoxic effects in C6 GBM cells. Biodistribution study in a rat GBM model demonstrated buildup of high CGT level in tumors subjected to CGT-NP+UTMD combined therapy. The tumor CGT level in these animals was increased over 3-fold, tumor retention of CGT prolonged and renal clearance significantly reduced when compared with free CGT with or without UTMD. CGT-NP+UTMD treatment was further shown to extend the median survival period from less than 2...Continue Reading

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Citations

Jan 24, 2017·Future Medicinal Chemistry·Aleksandra Ellert-MiklaszewskaBozena Kaminska
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Aug 10, 2021·International Journal of Pharmaceutics·Qing-Hua LanQing Yao
Sep 21, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Namita MahadikRajkumar Banerjee

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