title: Targeting glucose uptake with siRNA-based nanomedicine for cancer therapy.
abstract: Targeting cancer metabolism is emerging as a successful strategy for cancer therapy. However, most of the marketed anti-metabolism drugs in cancer therapy do not distinguish normal cells from cancer cells, leading to severe side effects. In this study, we report an effective strategy for cancer therapy through targeting glucose transporter 3 (GLUT3) with siRNA-based nanomedicine to simultaneously inhibit the self-renewal of glioma stem cells and bulk glioma cells in a glucose restricted tumor micro-environment. We have demonstrated that cationic lipid-assisted poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-PLA) nanoparticles can efficiently deliver siRNA into U87MG and U251 glioma stem cells and bulk glioma cells. Nanoparticles carrying specific siRNA targeting GLUT3 (NPsiGLUT3) were able to significantly reduce the expression of GLUT3 in glioma stem cells and bulk glioma cells, while GLUT3 knockdown results in obvious cell metabolism and proliferation inhibition, and further glioma stem cells percentage down-regulation. Moreover, systemic delivery of NPsiGLUT3, via intravenous injection, significantly inhibited tumor growth in a U87MG xenograft model, due to the reduced expression of GLUT3 and down-regulated stemness of glioma cells.
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, Anhui, China.
authors.forename: Cong-Fei
authors.initials: CF
authors.lastname: Xu
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, Anhui, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, Anhui, China.
authors.forename: Song
authors.initials: S
authors.lastname: Shen
authors.affiliation: The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, Anhui, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Zhu
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, Anhui, China; The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei 230027, Anhui, China. Electronic address: jwang699@ustc.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000473:pathology / Q000628:therapy*; D005947:Glucose / Q000378:metabolism*; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D050997:Nanomedicine; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D051274:Glucose Transporter Type 3; D034741:RNA, Small Interfering; D005947:Glucose
keywords: Cancer therapy; Glioma stem cells; Glucose transporter 3; Nanomedicine; siRNA delivery