title: Monoclonal antibody-functionalized multilayered particles: targeting cancer cells in the presence of protein coronas.
abstract: Engineered particles adsorb biomolecules (e.g., proteins) when introduced in a biological medium to form a layer called a "corona". Coronas, in particular the protein corona, play an important role in determining the surface properties of particles and their targeting abilities. This study examines the influence of protein coronas on the targeting ability of layer-by-layer (LbL)-assembled polymer capsules and core-shell particles functionalized with monoclonal antibodies. Upon exposure of humanized A33 monoclonal antibody (huA33 mAb)-functionalized poly(methacrylic acid) (PMA) capsules or huA33 mAb-PMA particles to human serum, a total of 83 or 65 proteins were identified in the protein coronas, respectively. Human serum of varying concentrations altered the composition of the protein corona. The antibody-driven specific cell membrane binding was qualitatively and quantitatively assessed by flow cytometry and fluorescence microscopy in both the absence and presence of a protein corona. The findings show that although different protein coronas formed in human serum (at different concentrations), the targeting ability of both the huA33 mAb-functionalized PMA capsules and particles toward human colon cancer cells was retained, demonstrating no significant difference compared with capsules and particles in the absence of protein coronas: ∼70% and ∼90% A33-expressing cells were targeted by the huA33 mAb-PMA capsules and particles, respectively, in a mixed cell population. This result demonstrates that the formation of protein coronas did not significantly influence the targeting ability of antibody-functionalized LbL-polymer carriers, indicating that the surface functionality of engineered particles in the presence of protein coronas can be preserved.
authors.affiliation: †ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Dai
authors.affiliation: †ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: ‡Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ching-Seng
authors.initials: CS
authors.lastname: Ang
authors.affiliation: †ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Kristian
authors.initials: K
authors.lastname: Kempe
authors.affiliation: †ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Marloes M J
authors.initials: MM
authors.lastname: Kamphuis
authors.affiliation: †ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dodds
authors.affiliation: †ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
mesh_terms: D000327:Adsorption; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry* / Q000276:immunology; D001798:Blood Proteins / Q000737:chemistry; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D011109:Polymethacrylic Acids / Q000737:chemistry; D011487:Protein Conformation; D000066970:Protein Corona / Q000737:chemistry*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D001798:Blood Proteins; D004337:Drug Carriers; C104258:GPA33 protein, human; D008562:Membrane Glycoproteins; D011109:Polymethacrylic Acids; D000066970:Protein Corona; C030613:polymethacrylic acid
keywords: human serum; layer-by-layer assembly; monoclonal antibody; polymer particles; protein corona; targeted drug delivery