Hydrophobic cargo loading at the core-corona interface of uniform, length-tunable aqueous diblock copolymer nanofibers with a crystalline polycarbonate core

1D core-shell nanoparticles are considered to be among the most promising for biomedical applications such as drug delivery. The versatile living crystallization-driven self-assembly (CDSA) seeded growth method allows access to uniform, length-tunable, and water-dispersible nanofibers from block copolymer (BCP) amphiphiles. A problem with respect to their use for drug delivery is that encapsulation of cargo within the crystalline core is expected to be difficult. Herein, we demonstrate that non-covalent hydrophobic cargo uptake by diBCP nanofibers with a crystalline poly(fluorenetrimethylenecarbonate) (PFTMC) core and a corona of either poly(N-isopropylacrylamide, PNIPAM) or poly(ethylene glycol, PEG) can be achieved at the core-corona interface. The length of the nanofibers was precisely controlled over a wide range of lengths (ca. 50-1700 nm, D < 1.07), however we focused on low dispersity nanofibers with lengths relevant for drug delivery (100-130 nm, D < 1.06) for cargo loading experiments. After loading via a solvent switch to water, the nanofibers remained colloidally stable for at least 6 months and for up to 48 h under enzymatic conditions, as observed by the absence of aggregation by TEM and DLS analysis. Our findings indicate that uptake of the hydrophobic fluorescent dye Nile Red, used as a proxy for a therapeutic cargo, is independent of the nature and length of the corona-forming blocks of the nanofibers. Localization of the cargo at the core-corona interface was evidenced by fluorescence spectroscopy and fluorescence lifetime measurements were also consistent with this assertion.