PEGylated Albumin based Polyion Complex Micelles for protein delivery

Jiang, Y; Lu, H; Chen, F; Callari, M; Pourgholami, M; Morris, DL; Stenzel, MH

PEGylated Albumin based Polyion Complex Micelles for protein delivery

Jiang, Y Lu, H

Chen, F Callari, M Pourgholami, M Morris, DL Stenzel, MH

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Publisher:: AMER CHEMICAL SOC
Publication Type:: Journal Article
Citation:: Biomacromolecules, 2016, 17, (3), pp. 808-817
Issue Date:: 2016

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Field	Value	Language
dc.contributor.author	Jiang, Y
dc.contributor.author	Lu, H https://orcid.org/0000-0001-6932-1900
dc.contributor.author	Chen, F
dc.contributor.author	Callari, M
dc.contributor.author	Pourgholami, M
dc.contributor.author	Morris, DL
dc.contributor.author	Stenzel, MH
dc.date.accessioned	2022-08-21T21:53:58Z
dc.date.available	2022-08-21T21:53:58Z
dc.date.issued	2016
dc.identifier.citation	Biomacromolecules, 2016, 17, (3), pp. 808-817
dc.identifier.issn	1525-7797
dc.identifier.issn	1526-4602
dc.identifier.uri	http://hdl.handle.net/10453/160623
dc.description.abstract	An increasing amount of therapeutic agents are based on proteins. However, proteins as drug have intrinsic problems such as their low hydrolytic stability. Delivery of proteins using nanoparticles has increasingly been the focus of interest with polyion complex micelles, prepared from charged block copolymer and the oppositely charged protein, as an example of an attractive carrier for proteins. Inspired by this approach, a more biocompatible pathway has been developed here, which replaces the charged synthetic polymer with an abundant protein, such as albumin. Although bovine serum albumin (BSA) was observed to form complexes with positively charged proteins directly, the resulting protein nanoparticle were not stable and aggregated to large precipitates over the course of a day. Therefore, maleimide functionalized poly(oligo (ethylene glycol) methyl ether methacrylate) (MI-POEGMEMA) (Mn = 26000 g/mol) was synthesized to generate a polymer-albumin conjugate, which was able to condense positively charged proteins, here lysozyme (Lyz) as a model. The PEGylated albumin polyion complex micelle with lysozyme led to nanoparticles between 15 and 25 nm in size depending on the BSA to Lyz ratio. The activity of the encapsulated protein was tested using Sprouty 1 (C-12; Spry1) proteins, which can act as an endogenous angiogenesis inhibitor. Condensation of Spry1 with the PEGylated albumin could improve the anticancer efficacy of Spry1 against the breast cancer cells lowering the IC50 value of the protein. Furthermore, the high anticancer efficacy of the POEGMEMA-BSA/Spry1 complex micelle was verified by effectively inhibiting the growth of three-dimensional MCF-7 multicellular tumor spheroids. The PEGylated albumin complex micelle has great potential as a drug delivery vehicle for a new generation of cancer pharmaceuticals.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER CHEMICAL SOC
dc.relation.ispartof	Biomacromolecules
dc.relation.isbasedon	10.1021/acs.biomac.5b01537
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	03 Chemical Sciences, 06 Biological Sciences, 09 Engineering
dc.subject.classification	Polymers
dc.subject.mesh	Drug Carriers
dc.subject.mesh	Enzyme Stability
dc.subject.mesh	Humans
dc.subject.mesh	MCF-7 Cells
dc.subject.mesh	Maleimides
dc.subject.mesh	Methacrylates
dc.subject.mesh	Micelles
dc.subject.mesh	Muramidase
dc.subject.mesh	Nanoparticles
dc.subject.mesh	Polyethylene Glycols
dc.subject.mesh	Serum Albumin, Bovine
dc.subject.mesh	Humans
dc.subject.mesh	Polyethylene Glycols
dc.subject.mesh	Methacrylates
dc.subject.mesh	Maleimides
dc.subject.mesh	Muramidase
dc.subject.mesh	Serum Albumin, Bovine
dc.subject.mesh	Drug Carriers
dc.subject.mesh	Enzyme Stability
dc.subject.mesh	Micelles
dc.subject.mesh	Nanoparticles
dc.subject.mesh	MCF-7 Cells
dc.title	PEGylated Albumin based Polyion Complex Micelles for protein delivery
dc.type	Journal Article
utslib.citation.volume	17
utslib.location.activity	United States
utslib.for	03 Chemical Sciences
utslib.for	06 Biological Sciences
utslib.for	09 Engineering
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	closed_access	*
dc.date.updated	2022-08-21T21:53:55Z
pubs.issue	3
pubs.publication-status	Published
pubs.volume	17
utslib.citation.issue	3

Abstract:

An increasing amount of therapeutic agents are based on proteins. However, proteins as drug have intrinsic problems such as their low hydrolytic stability. Delivery of proteins using nanoparticles has increasingly been the focus of interest with polyion complex micelles, prepared from charged block copolymer and the oppositely charged protein, as an example of an attractive carrier for proteins. Inspired by this approach, a more biocompatible pathway has been developed here, which replaces the charged synthetic polymer with an abundant protein, such as albumin. Although bovine serum albumin (BSA) was observed to form complexes with positively charged proteins directly, the resulting protein nanoparticle were not stable and aggregated to large precipitates over the course of a day. Therefore, maleimide functionalized poly(oligo (ethylene glycol) methyl ether methacrylate) (MI-POEGMEMA) (Mn = 26000 g/mol) was synthesized to generate a polymer-albumin conjugate, which was able to condense positively charged proteins, here lysozyme (Lyz) as a model. The PEGylated albumin polyion complex micelle with lysozyme led to nanoparticles between 15 and 25 nm in size depending on the BSA to Lyz ratio. The activity of the encapsulated protein was tested using Sprouty 1 (C-12; Spry1) proteins, which can act as an endogenous angiogenesis inhibitor. Condensation of Spry1 with the PEGylated albumin could improve the anticancer efficacy of Spry1 against the breast cancer cells lowering the IC50 value of the protein. Furthermore, the high anticancer efficacy of the POEGMEMA-BSA/Spry1 complex micelle was verified by effectively inhibiting the growth of three-dimensional MCF-7 multicellular tumor spheroids. The PEGylated albumin complex micelle has great potential as a drug delivery vehicle for a new generation of cancer pharmaceuticals.

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http://hdl.handle.net/10453/160623