Folic Acid Conjugated Amino Acid-Based Star Polymers for Active Targeting of Cancer Cells

• Published in: Biomacromolecules 2011-10, Vol.12 (10), p.3469-3477
• Main Authors: Sulistio, Adrian, Lowenthal, Justin, Blencowe, Anton, Bongiovanni, Marie N, Ong, Lydia, Gras, Sally L, Zhang, Xiaoqing, Qiao, Greg G
• Format: Article
• Language: English
• Subjects: Aminoacid polymers; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Applied sciences; Biocompatible Materials - analysis; Biocompatible Materials - chemical synthesis; Biocompatible Materials - pharmacology; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Survival - drug effects; Click Chemistry - methods; Cystine - chemistry; Drug Carriers - analysis; Drug Carriers - chemical synthesis; Drug Carriers - pharmacology; Exact sciences and technology; Female; Flow Cytometry; Fluorescent Dyes - analysis; Folic Acid - chemistry; General pharmacology; Humans; Medical sciences; Micelles; Microscopy, Confocal; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physicochemistry of polymers; Polyethylene Glycols - chemistry; Polylysine - chemistry; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Synthetic biopolymers
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm200604h

Amino acid-based core cross-linked star (CCS) polymers (poly(l-lysine)armpoly(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)armpoly(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.