title: Influence of size, surface, cell line, and kinetic properties on the specific binding of A33 antigen-targeted multilayered particles and capsules to colorectal cancer cells.
abstract: There has been increased interest in the use of polymer capsules formed by the layer-by-layer (LbL) technique as therapeutic carriers to cancer cells due to their versatility and ease of surface modification. We have investigated the influence of size, surface properties, cell line, and kinetic parameters such as dosage (particle concentration) and incubation time on the specific binding of humanized A33 monoclonal antibody (huA33 mAb)-coated LbL particles and capsules to colorectal cancer cells. HuA33 mAb binds to the A33 antigen present on almost all colorectal cancer cells and has demonstrated great promise in clinical trials as an immunotherapeutic agent for cancer therapy. Flow cytometry experiments showed the cell binding specificity of huA33 mAb-coated particles to be size-dependent, with the optimal size for enhanced selectivity at approximately 500 nm. The specific binding was improved by increasing the dosage of particles incubated with the cells. The level of specific versus nonspecific binding was compared for particles terminated with various polyelectrolytes to examine the surface dependency of antibody attachment and subsequent cell binding ability. The specific binding of huA33 mAb-coated particles is also reported for two colorectal cancer cell lines, with an enhanced binding ratio between 4 and 10 obtained for the huA33 mAb-functionalized particles. This investigation aims to improve the level of specific targeting of LbL particles, which is important in targeted drug and gene delivery applications.
authors.affiliation: Centre for Nanoscience and Nanotechnology, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Christina
authors.initials: C
authors.lastname: Cortez
authors.forename: Eva
authors.initials: E
authors.lastname: Tomaskovic-Crook
authors.forename: Angus P R
authors.initials: AP
authors.lastname: Johnston
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
authors.forename: Edouard C
authors.initials: EC
authors.lastname: Nice
authors.forename: Joan K
authors.initials: JK
authors.lastname: Heath
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D002214:Capsules; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D002214:Capsules; D005456:Fluorescent Dyes; C104258:GPA33 protein, human; D008562:Membrane Glycoproteins; D011108:Polymers