Safety of nanoparticles based on albumin-polymer conjugates as a carrier of nucleotides for pancreatic cancer therapy

Taguchi, K; Lu, H; Jiang, Y; Hung, TT; Stenzel, MH

Safety of nanoparticles based on albumin-polymer conjugates as a carrier of nucleotides for pancreatic cancer therapy

Taguchi, K Lu, H

Jiang, Y Hung, TT

Stenzel, MH

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Publication Type:: Journal Article
Citation:: Journal of Materials Chemistry B, 2018, 6 (39), pp. 6278 - 6287
Issue Date:: 2018-01-01

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Field	Value	Language
dc.contributor.author	Taguchi, K	en_US
dc.contributor.author	Lu, H https://orcid.org/0000-0001-6932-1900	en_US
dc.contributor.author	Jiang, Y	en_US
dc.contributor.author	Hung, TT https://orcid.org/0000-0002-2904-2664	en_US
dc.contributor.author	Stenzel, MH https://orcid.org/0000-0002-6433-4419	en_US
dc.date.issued	2018-01-01	en_US
dc.identifier.citation	Journal of Materials Chemistry B, 2018, 6 (39), pp. 6278 - 6287	en_US
dc.identifier.issn	2050-7518	en_US
dc.identifier.uri	http://hdl.handle.net/10453/132775
dc.description.abstract	© The Royal Society of Chemistry. Gene therapy through systemic administration is expected to offer significant therapeutic potential against intractable cancers, including pancreatic cancer. One of the requirements for in vivo gene therapy is the development of a gene carrier with a high level of safety, transfection ability and tumour accumulation. Bovine serum albumin (BSA)-poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) conjugation (BSA-PDMAEMA conjugation) could result in the development of a promising gene carrier. This conjugate could preserve the BSA structure well and efficiently condense the nucleotide inside, resulting in the formation of BSA-PDMAEMA nanoparticles that have a polyion complex core and surrounding BSA corona with a size of <100 nm. The nanoparticles that were produced based on BSA-PDMAEMA conjugation possessed good characteristics for use as a gene carrier with good biocompatibility, appropriate blood retention and gene protective properties. Furthermore, the in vivo two-dimensional and three-dimensional biodistribution in a xenograft pancreatic cancer (AsPC-1) model in mice clearly showed that BSA-PDMAEMA nanoparticles accumulated at the tumour site via enhanced permeability and the retention effect. Furthermore, BSA-PDMAEMA nanoparticles, which condensed the active anti-cancer oligonucleotide, ISIS5132, inhibited the growth of cancer in AsPC-1-bearing mice compared to mice which were administered with ISIS5132 alone. The structure of the BSA-PDMAEMA nanoparticles, i.e. the polyion complex core with the BSA corona, would comprehensively contribute to these ideal characteristics for use as a gene carrier. In conclusion, BSA-PDMAEMA nanoparticles could exert a therapeutic effect on intractable pancreatic cancer in vivo, indicating their use as a promising gene carrier.	en_US
dc.relation.ispartof	Journal of Materials Chemistry B	en_US
dc.relation.isbasedon	10.1039/C8TB01613E	en_US
dc.title	Safety of nanoparticles based on albumin-polymer conjugates as a carrier of nucleotides for pancreatic cancer therapy	en_US
dc.type	Journal Article
utslib.citation.volume	39	en_US
utslib.citation.volume	6	en_US
utslib.for	0303 Macromolecular and Materials Chemistry	en_US
utslib.for	0903 Biomedical Engineering	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	closed_access
pubs.issue	39	en_US
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

Abstract:

© The Royal Society of Chemistry. Gene therapy through systemic administration is expected to offer significant therapeutic potential against intractable cancers, including pancreatic cancer. One of the requirements for in vivo gene therapy is the development of a gene carrier with a high level of safety, transfection ability and tumour accumulation. Bovine serum albumin (BSA)-poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) conjugation (BSA-PDMAEMA conjugation) could result in the development of a promising gene carrier. This conjugate could preserve the BSA structure well and efficiently condense the nucleotide inside, resulting in the formation of BSA-PDMAEMA nanoparticles that have a polyion complex core and surrounding BSA corona with a size of <100 nm. The nanoparticles that were produced based on BSA-PDMAEMA conjugation possessed good characteristics for use as a gene carrier with good biocompatibility, appropriate blood retention and gene protective properties. Furthermore, the in vivo two-dimensional and three-dimensional biodistribution in a xenograft pancreatic cancer (AsPC-1) model in mice clearly showed that BSA-PDMAEMA nanoparticles accumulated at the tumour site via enhanced permeability and the retention effect. Furthermore, BSA-PDMAEMA nanoparticles, which condensed the active anti-cancer oligonucleotide, ISIS5132, inhibited the growth of cancer in AsPC-1-bearing mice compared to mice which were administered with ISIS5132 alone. The structure of the BSA-PDMAEMA nanoparticles, i.e. the polyion complex core with the BSA corona, would comprehensively contribute to these ideal characteristics for use as a gene carrier. In conclusion, BSA-PDMAEMA nanoparticles could exert a therapeutic effect on intractable pancreatic cancer in vivo, indicating their use as a promising gene carrier.

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http://hdl.handle.net/10453/132775