title: Star-branched amphiphilic PLA-b-PDMAEMA copolymers for co-delivery of miR-21 inhibitor and doxorubicin to treat glioma.
abstract: The combined treatment of chemotherapeutant and microRNA (miR) has been proven to be a viable strategy for enhancing chemosensitivity due to its synergistic effect for tumor therapy. However, the co-delivery of drugs and genes remains a major challenge as they lack efficient co-delivery carriers. In this study, three amphiphilic star-branched copolymers comprising polylactic acid (PLA) and polydimethylaminoethyl methacrylate (PDMAEMA) with AB3, (AB3)2,and (AB3)3 molecular architectures were synthesized respectively by a combination of ring-opening polymerization, atom transfer radical polymerization, and click chemistry via an "arm-first" approach. The star copolymers possessed a low critical micelle concentration (CMC) and formed nano-sized micelles with positive surface charges in water as well as exhibiting a much lower cytotoxicity than PEI 25 kDa. Nevertheless, their gene transfection efficiency and tumor inhibition ability showed a remarkable dependence on their molecular architecture. The (AB3)3 architecture micelle copolymer exhibited the highest transfection efficiency, about 2.5 times higher than PEI. In addition, after co-delivering DOX and miR-21 inhibitor (miR-21i) into LN229 glioma cells, the micelles could mediate escaping miR-21i from lysosome degradation and the release of DOX to the nucleus, which significantly decreased the miR-21 expression. Moreover, co-delivery of DOX and miR-21i surprisingly exhibited an anti-proliferative efficiency compared with DOX or the miR-21i treatment alone. These results demonstrated that amphiphilic star-branched copolymers are highly promising for their combinatorial delivery of genes and hydrophobic therapeutants.
authors: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072, China.
authors: Xiaomin
authors: X
authors: Qian
authors: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072, China.
authors: Lixia
authors: L
authors: Long
authors: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin 300052, China.
authors: Zhendong
authors: Z
authors: Shi
authors: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072, China.
authors: Chaoyong
authors: C
authors: Liu
authors: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin 300052, China.
authors: Mingzhe
authors: M
authors: Qiu
authors: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072, China.
authors: Jing
authors: J
authors: Sheng
authors: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin 300052, China.
authors: Peiyu
authors: P
authors: Pu
authors: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science & Engineering, Tianjin University, Tianjin 300072, China. Electronic address: xbyuan@tju.edu.cn.
authors: Xubo
authors: X
authors: Yuan
authors: Tianjin Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China. Electronic address: renyu_1212@yahoo.com.cn.
authors: Yu
authors: Y
authors: Ren
authors: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government, Tianjin 300052, China. Electronic address: kang97061@yahoo.com.
authors: Chunsheng
authors: C
authors: Kang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D017404:In Situ Hybridization, Fluorescence; D008689:Methacrylates / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors*; D046529:Microscopy, Electron, Transmission; D011091:Polyesters / Q000008:administration & dosage*
chemical_list: D000903:Antibiotics, Antineoplastic; C524940:MIRN21 microRNA, human; D008689:Methacrylates; D035683:MicroRNAs; D011091:Polyesters; C542831:poly(lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate); D004317:Doxorubicin
keywords: Co-delivery; Polydimethylaminoethyl methacrylate; Polylactic acid; Star-branched copolymer; Synergistic effects; miR-21