title: Enhanced Sensitivity of Cancer Stem Cells to Chemotherapy Using Functionalized Mesoporous Silica Nanoparticles.
abstract: Cancer stem cells (CSCs) are responsible for cancer drug resistance with high expression of ABCG2, which pumps the internalized chemotherapeutic out to escape drug-induced cytotoxicity. Here, we established a functionalized mesoporous silica nanoparticle (MSN) system to deliver shABCG2 and doxorubicin (Dox) synergistically. With excellent cell uptake and endosomal escape capacities, the dual-delivery carriers internalized shABCG2 and Dox into CSCs efficiently. ABCG2 depletion increased intracellular and intranuclear Dox enrichment, drove vigorous Dox-induced cell death, and impaired the self-renewal of CSCs. Additionally, the nanoparticles eliminated tumors efficiently and reduced tumor initiation by CSCs in vivo, with negligible side effects. Our findings suggest that well-designed delivery systems for conventional chemotherapeutic agents are promising for CSC therapy.
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou 450001, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Life Sciences, University of Science and Technology of China , Hefei, Anhui 230027, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Yushun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou 450001, China.
authors.forename: Yating
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province, College of Chemistry and Chemical Engineering, Lanzhou University , Lanzhou 730000, China.
authors.forename: Lifen
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Zhengzhou University , Zhengzhou 450001, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D009363:Neoplasm Proteins; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000970:Antineoplastic Agents; D004337:Drug Carriers; D009363:Neoplasm Proteins; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: cancer stem cells; dual delivery; mesoporous silica nanoparticles; shABCG2