title: Tumor Targeting Synergistic Drug Delivery by Self-Assembled Hybrid Nanovesicles to Overcome Drug Resistance.
abstract: To overcome multi-drug resistance (MDR) in tumor chemotherapy, a polymer/inorganic hybrid drug delivery platform with tumor targeting property and enhanced cell uptake efficiency was developed.
  
  
  
  To evaluate the applicability of our delivery platform for the delivery of different drug resistance inhibitors, two kinds of dual-drug pairs (doxorubicin/buthionine sulfoximine and doxorubicin/tariquidar, respectively) were loaded in heparin-biotin/heparin/protamine sulfate/calcium carbonate nanovesicles to realize simultaneous delivery of an anticancer drug and a drug resistance inhibitor into drug-resistant tumor cells.
  
  
  
  Prepared by self-assembly, the drug loaded hybrid nanovesicles with a mean size less than 210 nm and a negative zeta potential exhibit good stability in serum contained aqueous media. The in vitro cytotoxicity evaluation indicates that hybrid nanovesicles with tumor targeting biotin moieties have an enhanced tumor cell inhibitory effect. In addition, dual-drug loaded hybrid nanovesicles exhibit significantly stronger cell growth inhibition as compared with doxorubicin (DOX) mono-drug loaded nanovesicles due to the reduced intracellular glutathione (GSH) content by buthionine sulfoximine (BSO) or the P-glycoprotein (P-gp) inhibition by tariquidar (TQR).
  
  
  
  The tumor targeting nanovesicles prepared in this study, which can simultaneously deliver multiple drugs and effectively reverse drug resistance, have promising applications in drug delivery for tumor treatments. The polymer/inorganic hybrid drug delivery platform developed in this study has good applicability for the co-delivery of different anti-tumor drug/drug resistance inhibitor pairs to overcome MDR. Graphical Abstract A polymer/inorganic hybrid drug delivery platform with enhanced cell uptake was developed for tumor targeting synergistic drug delivery. The heparin-biotin/heparin/protamine sulfate/calcium carbonate nanovesicles prepared in this study can deliver an anticancer drug and a drug resistance inhibitor into drug-resistant tumor cells simultaneously to overcome drug resistance efficiently.
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Meng-Qing
authors.initials: MQ
authors.lastname: Gong
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: He
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Zong
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Wu
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, People's Republic of China.
authors.forename: Ren-Xi
authors.initials: RX
authors.lastname: Zhuo
authors.affiliation: Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, 430072, People's Republic of China. chengsixue@whu.edu.cn.
authors.forename: Si-Xue
authors.initials: SX
authors.lastname: Cheng
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001710:Biotin / Q000737:chemistry; D019328:Buthionine Sulfoximine / Q000008:administration & dosage; D002119:Calcium Carbonate / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D006493:Heparin / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry; D011479:Protamines / Q000737:chemistry; D011804:Quinolines / Q000008:administration & dosage
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D011479:Protamines; D011804:Quinolines; D019328:Buthionine Sulfoximine; D001710:Biotin; D004317:Doxorubicin; D006493:Heparin; D005978:Glutathione; D002119:Calcium Carbonate; C402343:tariquidar
keywords: drug delivery; hybrid nanovesicles; multi-drug resistance; natural polymers