Rodlike Block Copolymer Micelles of Controlled Length in Water Designed for Biomedical Applications

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-PAPMA(3)-stat-OEGMA(48)). 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 (L-w/L-n < 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.