Author/Authors :
Mizushima, Ryota Department of Medical Physics and Engineering - Division of Health Sciences - Graduate School of Medicine - Osaka University - Suita - Osaka, Japan , Inoue, Kanako Osaka University - Suita - Osaka, Japan , Fujiwara, Hideaki Department of Medical Physics and Engineering - Division of Health Sciences - Graduate School of Medicine - Osaka University - Suita - Osaka, Japan , Iwane, Atsuko H Higashi-Hiroshima - Hiroshima, Japan , Watanabe, Tomonobu M Riken - Suita - Osaka, Japan , Kimura, Atsuomi Department of Medical Physics and Engineering - Division of Health Sciences - Graduate School of Medicine - Osaka University - Suita - Osaka, Japan
Abstract :
Gas vesicle nanoparticles (GVs) are gas-containing protein assemblies expressed in bacteria and archaea. Recently, GVs have
gained considerable attention for biotechnological applications as genetically encodable contrast agents for MRI and ultrasonography. However, at present, the practical use of GVs is hampered by a lack of robust methodology for their induction into
mammalian cells. Here, we demonstrate the genetic reconstitution of protein nanoparticles with characteristic bicone structures
similar to natural GVs in a human breast cancer cell line KPL-4 and genetic control of their size and shape through expression of
reduced sets of humanized gas vesicle genes cloned into Tol2 transposon vectors, referencing the natural gas vesicle gene clusters
of the cyanobacteria planktothrix rubescens/agardhii. We then report the utility of these nanoparticles as multiplexed, sensitive,
and genetically encoded contrast agents for hyperpolarized xenon chemical exchange saturation transfer (HyperCEST) MRI.