Precision polymer nanofibers with a responsive polyelectrolyte corona designed as a modular, functionalizable nanomedicine platform

We describe the development of a modular, functionalizable platform for biocompatible core–shell block copolymer nanofibers of controlled length (22 nm–1.3 μm) and low dispersity produced via living crystallization-driven self-assembly (CDSA). The nanofibers possessed a crystalline poly(fluorenetrimethylenecarbonate) (PFTMC) core and a basic poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) corona. We demonstrate that the coronal chain terminus can be easily modified to incorporate imaging agents such as BODIPY dyes, and targeting groups such as folic acid (FA). Segmented and random block comicelle nanofibers with spatially defined or mixed coronal terminal groups provided further opportunities for tailoring nanofiber surface chemistry. The PDMAEMA corona was shown to be both pH- and thermo-responsive. Nanospheres were also produced by suppressing crystallization of the PFTMC core during self-assembly and these facilitated studies into the effects of particle morphology. In vitro studies on the enzymatic degradation of PFTMC16-b-PDMAEMA131 nanofibers and nanospheres using lipase revealed that short nanofibers degraded over three times slower than nanospheres. The cytotoxicity of PFTMC16-b-PDMAEMA131 nanofibers and nanospheres was compared to PDMAEMA homopolymer and branched polyethyleneimine using WI-38 and HeLa cells and appeared to be primarily influenced by surface chemistry, with particle morphology a secondary factor. These results lay the groundwork for the future development of precision polymer nanofibers that may find use in several applications, from the delivery of nucleic acids into cells, to uses as lubricants or as surface coatings. In particular, this system may enable fundamental studies on the effects of particle morphology on nucleic acid delivery.