Comparison of Nanoreactor Efficiency for Peroxyoxalate Chemiluminescent Reaction in Aqueous Medium

Abstract

The peroxyoxalate chemiluminescent reaction is an excellent source of excitation for photosensitizers used in theranostics for identification and targeting of tumor cells that produce elevated amounts of hydrogen peroxide. However, the substrates of peroxyoxalate chemiluminescent reaction, aromatic oxalates, are highly susceptible to hydrolysis in aqueous surroundings. Solubilization of oxalates in nanoreactors with a hydrophobic core significantly reduces their degradation by water. In this study, we compared for the first time the efficiency of the peroxyoxalate chemiluminescent reaction in emulsion and micellar nanoreactors. Two oxalates were studied herein, i.e. a highly active bis(2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl) oxalate (CPPO) and nearly 15-fold less active but bioinspired tyrosine-based oxalate (BTEE-ox), which differed significantly in the pK_a of the leaving phenolic group, cytotoxicity, and hydrophobicity. Encapsulation of both oxalates into emulsion nanoreactors increased stability of both oxalates approximately by two orders of magnitude as compared to a THF/water (4 : 1) homogeneous solution. However, the emulsion underwent colloidal destabilization due to Ostwald ripening. In contrast, polylactide-block-poly(ethylene glycol) micelles exhibited excellent colloidal stability and ensured low rate of oxalates hydrolysis. The chemiluminescence activity of BTEE-ox solubilized in micelles became even higher than that of CPPO indicating that solid nanoreactors influenced the peroxyoxalate chemiluminescent reaction efficiency.