title: PEGylated Albumin-Based Polyion Complex Micelles for Protein Delivery.
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.
authors.affiliation: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales UNSW , Kensington, NSW 2052, Australia.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales UNSW , Kensington, NSW 2052, Australia.
authors.forename: Hongxu
authors.initials: H
authors.lastname: Lu
authors.affiliation: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales UNSW , Kensington, NSW 2052, Australia.
authors.forename: Fan
authors.initials: F
authors.lastname: Chen
authors.affiliation: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales UNSW , Kensington, NSW 2052, Australia.|Liverpool Hospital Clinical School, and Molecular Medicine Research Group, University of Western Sydney , Sydney, NSW 2170, Australia.
authors.forename: Manuela
authors.initials: M
authors.lastname: Callari
authors.affiliation: Cancer Research Laboratory, Department of Surgery, St. George Hospital , Sydney, NSW 2217, Australia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Pourgholami
authors.affiliation: Cancer Research Laboratory, Department of Surgery, St. George Hospital , Sydney, NSW 2217, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Morris
authors.affiliation: Centre for Advanced Macromolecular Design, School of Chemistry and School of Chemical Engineering, University of New South Wales UNSW , Kensington, NSW 2052, Australia.
authors.forename: Martina H
authors.initials: MH
authors.lastname: Stenzel
mesh_terms: D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D004795:Enzyme Stability; D006801:Humans; D061986:MCF-7 Cells; D008301:Maleimides / Q000737:chemistry; D008689:Methacrylates / Q000737:chemistry*; D008823:Micelles; D009113:Muramidase / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008301:Maleimides; D008689:Methacrylates; D008823:Micelles; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D009113:Muramidase