Micelles based on a poly(2-oxazoline) triblock copolymer containing a pure stereoisomer E or Z-tetraphenylethylene core for theranostic applications

Abstract

Poly(2-oxazoline)s (POx) are among the most promising hydrophilic polymers that can act as a replacement for the overly used poly(ethylene glycol)s (PEG). POx are widely studied due to their similar properties to PEG, such as low toxicity, neutrality and stealth properties, when used as a coating for nanoparticles. In this work, micelles based on a POx triblock copolymer containing a E or Z-tetraphenylethylene (TPE) derivative core were successfully prepared. The physico-chemical properties of both stereochemically pure E/Z-micelles were compared throughout the study, ranging from their hydrodynamic size, aggregation-induced emission property and colloidal stability. Their ability to host hydrophobic molecules was studied in vitro using HeLa cancer cells by encapsulating the hydrophobic fluorophore 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) or anticancer drug 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX). The Förster resonance energy transfer (FRET) pair TPE-DiI displayed an efficient energy transfer process, as demonstrated by the increase in fluorescence, suggesting the effective cellular internalization of the micelles and making them a potential tool for dual imaging applications. The encapsulation and release of the neoplastic drug NBDHEX, known as a potent glutathione S-transferase P1-1 inhibitor, highlighted the major differences in the capacity for delivering NBDHEX between the E/Z-micelles, emphasizing the importance of controlling the configuration of the TPE unit core in theranostic applications.