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Title: Doxorubicin Delivered via ApoE-Directed Reduction-Sensitive Polymersomes Potently Inhibit Orthotopic Human Glioblastoma Xenografts in Nude Mice. Author: Ouyang J, Jiang Y, Deng C, Zhong Z, Lan Q. Journal: Int J Nanomedicine; 2021; 16():4105-4115. PubMed ID: 34163162. Abstract: PURPOSE: Glioblastoma multiforme (GBM) poorly responds to chemotherapy owing to the existence of blood-brain barriers (BBB). It has been a long desire to develop BBB-permeable vehicles to facilitate drug targeting to GBM. METHOD AND RESULTS: Here, we report that doxorubicin hydrochloride loaded in ApoE peptide-functionalized reduction-sensitive polymersomes (ApoE-PS-DOX) induces potent therapy of orthotopic U-87 MG model in nude mice. ApoE-PS-DOX with varying amount of ApoE (10~30 mol%) all had stable DOX loading and small sizes (< 90 nm). As revealed by flow cytometry, confocal microscopy, apoptosis and MTT assays, ApoE-PS-DOX with 20 mol.% ApoE induced the best cellular uptake and inhibitory effect to U-87 MG cells, which were much better than the non-targeted PS-DOX and liposomal doxorubicin (Lipo-DOX) used in the clinic. ApoE-PS-DOX revealed a pharmacokinetic profile comparable to PS-DOX but induced considerably better growth inhibition of orthotopically xenografted U-87 MG tumors in nude mice than PS-DOX and Lipo-DOX, leading to significant survival benefits with a median survival time of 44 days, which was almost doubled relative to the phosphate-buffered saline (PBS) group. Moreover, in contrast to mice treated with Lipo-DOX and PS-DOX, ApoE-PS-DOX group exhibited little body weight loss, signifying that ApoE-PS-DOX not only has low side effects but also can effectively inhibit glioblastoma invasion. CONCLUSION: This ApoE-docked multifunctional polymersomal doxorubicin induces potent and safe chemotherapy of orthotopic U-87 MG model in nude mice offering an alternative treatment modality for GBM.[Abstract] [Full Text] [Related] [New Search]