Rodlike Block Copolymer Micelles of Controlled Length in Water Designed for Biomedical Applications
- Qing YuQing YuDepartment of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, CanadaMore by Qing Yu,
- Megan G. RobertsMegan G. RobertsDepartment of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, CanadaMore by Megan G. Roberts,
- Samuel Pearce ,
- Alex M. OliverAlex M. OliverSchool of Chemistry, University of Bristol, Bristol BS8 1TS, U.K.More by Alex M. Oliver,
- Hang ZhouHang ZhouDepartment of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, CanadaMore by Hang Zhou,
- Christine AllenChristine AllenLeslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street, Toronto, Ontario M5S 3M2, CanadaMore by Christine Allen,
- Ian MannersIan MannersSchool of Chemistry, University of Bristol, Bristol BS8 1TS, U.K.Department of Chemistry, University of Victoria, Victoria, British Columbia V8W 3V6, CanadaMore by Ian Manners, and
- Mitchell A. Winnik*Mitchell A. Winnik*E-mail: [email protected]Department of Chemistry, Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, CanadaMore by Mitchell A. Winnik
Abstract

There is a broad interest in elongated colloids as drug delivery vehicles, and current research aims to address how their length and aspect ratio affect interactions with cells. Block copolymer (BCP) micelles offer the opportunity to vary micelle length while maintaining cross-sectional width with corona chains that maintain a common surface chemistry across these structures. However, most elongated BCP micelles used in cell studies are characterized by a very broad length distribution. Here, we describe the synthesis and self-assembly properties of a diblock copolymer with a polyferrocenylsilane core-forming block and a corona block consisting of a statistical polymer of (aminopropyl)methacrylamide and oligo(ethylene glycol methacrylate) (M = 500) (PFS27-b-PAPMA3-stat-OEGMA48). Self-assembly in water gave a mixture of structures including rodlike micelles. In alcohols, different types of structures were obtained depending on the alcohol employed (butanol, 2-propanol, ethanol, and methanol). In ethanol, the polymer formed long micelles of uniform width by crystallization-driven self-assembly. Following sonication, a series of rodlike micelles with different lengths (80 to 2000 nm) and narrow length distributions (Lw/Ln < 1.10) were generated by seeded growth. These micelles could be transferred to aqueous media and maintained colloidally stable in PBS (phosphate-buffered saline) buffer for more than three months. In these micelles, the POEGMA brush provides a “stealth” coating to minimize the interaction with proteins and cells, and the APMA groups provide functionality for attachment of drugs or metal chelators for potential therapeutic applications. Studies in two human breast cancer cell lines (MDA-MB-231 and MDA-MB-436) show no signs of toxicity for micelle concentrations up to 0.1 mg·mL–1. We also show that metal chelators can be covalently attached to the amino groups in the corona and labeled with heavy metals, opening the door to future experiments with radionuclides.




