title: Folic acid conjugated amino acid-based star polymers for active targeting of cancer cells.
abstract: Amino acid-based core cross-linked star (CCS) polymers (poly(L-lysine)(arm)poly(L-cystine)(core)) with peripheral allyl functionalities were synthesized by sequential ring-opening polymerization (ROP) of amino acid N-carboxyanhydrides (NCAs) via the arm-first approach, using N-(trimethylsilyl)allylamine as the initiator. Subsequent functionalization with a poly(ethylene glycol) (PEG)-folic acid conjugate via thiol-ene click chemistry afforded poly(PEG-b-L-lysine)(arm)poly(L-cystine)(core) stars with outer PEG coronas decorated with folic acid targeting moieties. Similarly, a control was prepared without folic acid, using just PEG. A fluorophore was used to track both star polymers incubated with breast cancer cells (MDA-MB-231) in vitro. Confocal microscopy and flow cytometry revealed that the stars could be internalized into the cells, and higher cell internalization was observed when folic acid moieties were present. Cytotoxicity studies indicate that both stars are nontoxic to MDA-MB-231 cells at concentrations of up to 50 μg/mL. These results make this amino acid-based star polymer an attractive candidate in targeted drug delivery applications including chemotherapy.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Melbourne, Parkville, Melbourne, VIC 3010, Australia.
authors.forename: Adrian
authors.initials: A
authors.lastname: Sulistio
authors.forename: Justin
authors.initials: J
authors.lastname: Lowenthal
authors.forename: Anton
authors.initials: A
authors.lastname: Blencowe
authors.forename: Marie N
authors.initials: MN
authors.lastname: Bongiovanni
authors.forename: Lydia
authors.initials: L
authors.lastname: Ong
authors.forename: Sally L
authors.initials: SL
authors.lastname: Gras
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Greg G
authors.initials: GG
authors.lastname: Qiao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry / Q000379:methods*; D003553:Cystine / Q000737:chemistry*; D004337:Drug Carriers / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000032:analysis; D005492:Folic Acid / Q000737:chemistry*; D006801:Humans; D008823:Micelles; D018613:Microscopy, Confocal; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008823:Micelles; D011107:Polylysine; D011092:Polyethylene Glycols; D003553:Cystine; D005492:Folic Acid