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Angiopep2-Conjugated Star-Shaped Polyprodrug Amphiphiles for Simultaneous Glioma-Targeting Therapy and MR Imaging

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journal contribution
posted on 02.03.2020, 05:29 by Xiao Wang, Guhuan Liu, Ni Chen, Jing Wu, Jingjing Zhang, Yinfeng Qian, Lei Zhang, Dandan Zhou, Yongqiang Yu
The development of valuable theranostic agents for overcoming the blood–brain barrier (BBB) to achieve efficient imaging-guided glioma-targeting delivery of therapeutics remains a great challenge for personalized glioma therapy. We herein developed a novel functional star-shaped polyprodrug amphiphile (denoted as CPP-2) via a combination of successive reversible addition–fragmentation chain transfer (RAFT) polymerization and click functionalization. In a diluted solution, the star amphiphile existed as structurally stable unimolecular micelles, containing hydrophobic cores conjugated with reduction-responsive camptothecin prodrugs Camptothecin (CPT) prodrug monomer (CPTM) and a tertiary amine monomer (2-(diethylamine) ethyl methacrylate, DEA) and hydrophilic oligo-(ethylene glycol) monomethyl ether methacrylat (OEGMA) outer coronas covalently decorated with dual-targeting moieties Angiopep2 (ANG) and small magnetic resonance imaging (MRI) contrast agents DOTA-Gd. In vitro and in vivo data in this study demonstrated that the ANG-modified micelles were capable of efficiently penetrating the BBB and delivering loaded cargoes such as CPT and Gd3+ contrast agents to glioma cells, leading to a considerably enhanced t1 relaxivity as well as antiglioma efficacy. Simultaneously, the targeted antiglioma efficacy and noninvasive MR imaging for a visualized therapy were realized. These collective findings augured well for the star polyprodrug amphiphiles to be utilized as a novel theranostic platform for clinical application in glioma therapy.