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Bioengineering novel floating nanoparticles for protein and drug delivery.

ABSTRACT: Gas vesicle nanoparticles (GVNPs) are hollow protein nanoparticles produced by Halobacterium sp. NRC-1 which are being engineered for protein delivery. To advance the bioengineering potential of GVNPs, a strain of NRC-1 deleted for the gvpC gene (?gvpC) was constructed and a synthetic gene coding for Gaussia princeps luciferase was fused to an abbreviated gvpC gene on an expression plasmid. When introduced into the?gvpC strain, an active GvpC-luciferase fusion protein bound to GVNPs resulted. These results represent both a technical improvement in the GVNP display system and its expansion for the display of active enzymes.

SUBMITTER: DasSarma P

PROVIDER: S-EPMC4856160 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Bioengineering novel floating nanoparticles for protein and drug delivery.

DasSarma Priya P Karan Ram R Kim Jong-Myoung JM Pecher Wolf W DasSarma Shiladitya S

Materials today. Proceedings 20160101 2

Gas vesicle nanoparticles (GVNPs) are hollow protein nanoparticles produced by Halobacterium sp. NRC-1 which are being engineered for protein delivery. To advance the bioengineering potential of GVNPs, a strain of NRC-1 deleted for the gvpC gene (ΔgvpC) was constructed and a synthetic gene coding for Gaussia princeps luciferase was fused to an abbreviated gvpC gene on an expression plasmid. When introduced into theΔgvpC strain, an active GvpC-luciferase ...[more]

PMID: 27158595

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Project description:The development of Drug Delivery Systems (DDS) has led to increasingly efficient therapies for the treatment and detection of various diseases. DDS use a range of nanoscale delivery platforms produced from polymeric of inorganic materials, such as micelles, and metal and polymeric nanoparticles, but their variant chemical composition make alterations to their size, shape, or structures inherently complex. Genetically encoded protein nanocages are highly promising DDS candidates because of their modular composition, ease of recombinant production in a range of hosts, control over assembly and loading of cargo molecules and biodegradability. One example of naturally occurring nanocompartments are encapsulins, recently discovered bacterial organelles that have been shown to be reprogrammable as nanobioreactors and vaccine candidates. Here we report the design and application of a targeted DDS platform based on the Thermotoga maritima encapsulin reprogrammed to display an antibody mimic protein called Designed Ankyrin repeat protein (DARPin) on the outer surface and to encapsulate a cytotoxic payload. The DARPin9.29 chosen in this study specifically binds to human epidermal growth factor receptor 2 (HER2) on breast cancer cells, as demonstrated in an in vitro cell culture model. The encapsulin-based DDS is assembled in one step in vivo by co-expressing the encapsulin-DARPin9.29 fusion protein with an engineered flavin-binding protein mini-singlet oxygen generator (MiniSOG), from a single plasmid in Escherichia coli. Purified encapsulin-DARPin_miniSOG nanocompartments bind specifically to HER2 positive breast cancer cells and trigger apoptosis, indicating that the system is functional and specific. The DDS is modular and has the potential to form the basis of a multi-receptor targeted system by utilising the DARPin screening libraries, allowing use of new DARPins of known specificities, and through the proven flexibility of the encapsulin cargo loading mechanism, allowing selection of cargo proteins of choice.

Dataset Information

Bioengineering novel floating nanoparticles for protein and drug delivery.

Publications

Bioengineering novel floating nanoparticles for protein and drug delivery.

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