title: Magnetically and pH dual responsive dendrosomes for tumor accumulation enhanced folate-targeted hybrid drug delivery.
abstract: Dendrosomes are new tumor targeted drug delivery systems to improve safety and therapeutic effects of antitumor agents. In this study we designed and synthesized magnetically and pH dual responsive dendrosomes with magnetic nanoparticles and folate-targeted dendrimers encapsulated in long-circulating pH sensitive liposomes. Cellular uptake and tissue penetration were assessed on cell lines and tumor spheroids respectively. Xenograft mice were used to study tumor accumulation. The dendrosomes were stable at pH7.4, but responsively released their content at acidic pH. In slightly acid environments, the hybrid vectors showed similar cytotoxicity and cellular uptake to the free folate-dendrimers conjugate due to rapid release. The dendrosomes showed a greater cellular uptake by HeLa cells (FA receptor positive) due to the conjugation with folic acid (FA). In multicellular tumor spheroid tests, a slightly acidic environment and the application of magnet both promoted the permeation efficiency of the hybrid vectors. In the xenograft mice model both in vivo images and tissue distribution assessment indicated that the dendrosomes had higher peak intensity and a longer residence time. Through the synergistic effects of magnetic responsiveness and both passive and active targeting properties, the multi-functional dendrosomes were demonstrated to have great potential as a promising anticancer drug delivery platform.
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Mu
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, Shandong Province, PR China; School of Pharmacy, Binzhou Medical University, Yantai, PR China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Chu
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China.
authors.forename: Zimei
authors.initials: Z
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, PR China. Electronic address: sunkx@ytu.edu.cn.
authors.forename: Kaoxiang
authors.initials: K
authors.lastname: Sun
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D060328:Magnetic Phenomena; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000378:metabolism*; D012235:Rhodamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D050091:Dendrimers; D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; C104700:PAMAM Starburst; D012235:Rhodamines; D005492:Folic Acid; C027755:rhodamine isothiocyanate
keywords: Dendrimer; Dendrosomes; Folic acid; Liposomes; Penetration; Tumor targeting