title: Oncolytic Adenovirus Complexes Coated with Lipids and Calcium Phosphate for Cancer Gene Therapy.
abstract: Oncolytic adenovirus (OncoAd) is a promising therapeutic agent for treating cancer. However, the therapeutic potential of OncoAdis hindered by hepatic sequestration and the host immune response in vivo. Here, we constructed a PEG/Lipids/calcium phosphate (CaP)-OncoAd(PLC-OncoAd) delivery system for ZD55-IL-24, an oncolytic adenovirus that carries the IL-24 gene. The negatively charged PLC-ZD55-IL-24 were disperse and resisted serum-induced aggregation. Compared to naked ZD55-IL-24, the systemic administration of PLC-ZD55-IL-24 in BALB/c mice resulted in reduced liver sequestration and systemic toxicity and evaded the innate immune response. In addition, masking the surface of OncoAdprotected it from neutralization by pre-existing neutralizing antibody. PLC-OncoAdachieved efficient targeted delivery in Huh-7-bearing nude mice, and intravenous administration of a high dose of PLC-ZD55-IL-24 increased therapeutic efficacy without inducing toxicity. The developed PLC-OncoAddelivery system represents a promising improvement for oncolytic adenovirus-based cancer gene therapy in vivo.
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China.
authors.forename: Sujing
authors.initials: S
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032, China.
authors.forename: Rongxin
authors.initials: R
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, China.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai 200032, China.
authors.forename: Yourong
authors.identifier: 0000-0002-3781-7845
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002130:Calcium Phosphates; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D005822:Genetic Vectors; D008055:Lipids; D051379:Mice; D008819:Mice, Nude; D050130:Oncolytic Virotherapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D002130:Calcium Phosphates; D008055:Lipids
keywords: calcium phosphate (CaP); cancer gene therapy; liver sequestration; oncolytic adenovirus; preexisting immunity; systemic administration