title: Targeting cancer cells: controlling the binding and internalization of antibody-functionalized capsules.
abstract: The development of nanoengineered particles, such as polymersomes, liposomes, and polymer capsules, has the potential to offer significant advances in vaccine and cancer therapy. However, the effectiveness of these carriers has the potential to be greatly improved if they can be specifically delivered to target cells. We describe a general method for functionalizing nanoengineered polymer capsules with antibodies using click chemistry and investigate their interaction with cancer cells in vitro. The binding efficiency to cells was found to be dependent on both the capsule-to-cell ratio and the density of antibody on the capsule surface. In mixed cell populations, more than 90% of target cells bound capsules when the capsule-to-target cell ratio was 1:1. Strikingly, greater than 50% of target cells exhibited capsules on the cell surface even when the target cells were present as less than 0.1% of the total cell population. Imaging flow cytometry was used to quantify the internalization of the capsules, and the target cells were found to internalize capsules efficiently. However, the role of the antibody in this process was determined to enhance accumulation of capsules on the cell surface rather than promote endocytosis. This represents a significant finding, as this is the first study into the role antibodies play in internalization of such capsules. It also opens up the possibility of targeting these capsules to cancer cells using targeting molecules that do not trigger an endocytic pathway. We envisage that this approach will be generally applicable to the specific targeting of a variety of nanoengineered materials to cells.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Melbourne, Victoria 3010, Australia. angusj@unimelb.edu.au
authors.forename: Angus P R
authors.initials: AP
authors.lastname: Johnston
authors.forename: Marloes M J
authors.initials: MM
authors.lastname: Kamphuis
authors.forename: Georgina K
authors.initials: GK
authors.lastname: Such
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: D000906:Antibodies / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000276:immunology*; D006801:Humans; D008422:Materials Testing; D008562:Membrane Glycoproteins / Q000276:immunology*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011485:Protein Binding
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; C104258:GPA33 protein, human; D008562:Membrane Glycoproteins; D053769:Nanocapsules