title: In vivo study of immunogenicity and kinetic characteristics of a quantum dot-labelled baculovirus.
abstract: Nanomaterials conjugated with biomacromolecules, including viruses, have great potential for in vivo applications. Therefore, it is important to evaluate the safety of nanoparticle-conjugated macromolecule biomaterials (Nano-mbio). Although a number of studies have assessed the risks of nanoparticles and macromolecule biomaterials in living bodies, only a few of them investigated Nano-mbios. Here we evaluated the in vivo safety profile of a quantum dot-conjugated baculovirus (Bq), a promising new Nano-mbio, in mice. Each animal was injected twice intraperitoneally with 50 μg virus protein labelled with around 3*10(-5)nmol conjugated qds. Control animals were injected with PBS, quantum dots, baculovirus, or a mixture of quantum dots and baculovirus. Blood, tissues and body weight were analysed at a series of time points following both the first and the second injections. It turned out that the appearance and behaviour of the mice injected with Bq were similar to those injected with baculovirus alone. However, combination of baculovirus and quantum dot (conjugated or simply mixed) significantly induced stronger adaptive immune responses, and lead to a faster accumulation and longer existence of Cd in the kidneys. Thus, despite the fact that both quantum dot and baculovirus have been claimed to be safe in vivo, applications of Bq in vivo should be cautious. To our knowledge, this is the first study examining the interaction between a nanoparticle-conjugated virus and a living body from a safety perspective, providing a basis for in vivo application of other Nano-mbios.
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China. Electronic address: zhengzh@wh.iov.cn.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Meng
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Man
authors.initials: M
authors.lastname: He
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Fuxian
authors.initials: F
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
authors.forename: Zike
authors.initials: Z
authors.lastname: He
authors.affiliation: State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Qinxue
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China. Electronic address: wanghz@wh.iov.cn.
authors.forename: Hanzhong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000210:Acute-Phase Reaction / Q000209:etiology; D056704:Adaptive Immunity; D000818:Animals; D016367:Baculoviridae / Q000276:immunology*; D001522:Behavior, Animal; D019921:Biotinylation; D019187:Cadmium Compounds / Q000032:analysis / Q000493:pharmacokinetics; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007668:Kidney / Q000737:chemistry; D008214:Lymphocytes / Q000276:immunology; D053768:Metal Nanoparticles / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates / Q000009:adverse effects; D057145:Nanoshells; D045663:Quantum Dots / Q000009:adverse effects; D018036:Selenium Compounds / Q000032:analysis / Q000493:pharmacokinetics; D013154:Spleen / Q000166:cytology; D015431:Weight Loss
chemical_list: D019187:Cadmium Compounds; D016207:Cytokines; D058726:Nanoconjugates; D018036:Selenium Compounds; D007371:Interferon-gamma; C058667:cadmium selenide
keywords: Immune response; Kinetic characteristic; Mice; Quantum dot-conjugated baculovirus (Bq); Toxicity