title: Macromolecule functionalization of disulfide-bonded polymer hydrogel capsules and cancer cell targeting.
abstract: We present a generic and versatile method for functionalization of disulfide-stabilized PMA hydrogel capsules (HCs) with macromolecules, including a number of specific antibodies to cancer cells. Functionalization was achieved by reversible addition-fragmentation chain transfer (RAFT) polymerization of poly(N-vinyl pyrrolidone) (PVPON), which introduced biorelevant heterotelechelic end groups (thiol and amine) to the polymer chain. The PVPON with heterotelechelic end groups was conjugated to the outermost layer of PMA HCs through the thiol groups and reacted with biotin via the amine groups to generate PMA/PVPON(biotin) HCs. On the basis of the high specific interaction and high affinity between biotin and avidin, and its derivates, such as NeutrAvidin (NAv), we functionalized the PMA HCs with biotinylated antibodies. We demonstrate significantly enhanced cellular binding and internalization of the antibody (Ab)-functionalized capsules compared with control human immunoglobulin (IgG)-functionalized capsules, suggesting these capsules can specifically interact with cells through antibody/antigen recognition. We anticipate that the versatility of the functionalization approach reported in this study will assist in targeted therapeutic delivery applications.
authors.affiliation: Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Olga
authors.initials: O
authors.lastname: Shimoni
authors.forename: Almar
authors.initials: A
authors.lastname: Postma
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
authors.forename: Joan K
authors.initials: JK
authors.lastname: Heath
authors.forename: Edouard C
authors.initials: EC
authors.lastname: Nice
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Zelikin
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
mesh_terms: D000906:Antibodies / Q000737:chemistry* / Q000378:metabolism; D001360:Avidin / Q000378:metabolism; D001710:Biotin / Q000378:metabolism; D002214:Capsules; D045744:Cell Line, Tumor; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D058105:Polymerization; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*
chemical_list: D000906:Antibodies; D002214:Capsules; D004220:Disulfides; D004337:Drug Carriers; D020100:Hydrogels; D011109:Polymethacrylic Acids; D001360:Avidin; C030613:polymethacrylic acid; D001710:Biotin; D011205:Povidone