Self-assembly prepared using an ion pair of poly(ethylene imine) and (phenylthio) acetic acid as a drug carrier for oxidation, temperature, and NIR-responsive release

Abstract

Poly(ethylene imine)/(phenylthio) acetic acid (PEI/PTA) ion pair whose the molar ratio of amino to carboxyl group ratio was 3/7 exhibited its upper critical solution temperature (UCST) around body temperature (37 ℃) at pH 7.0. The UCST decreased with increasing H2O2 concentration used to treat the ion pair (0 to 20 mM). Below the UCST, PEI/PTA ion pair was self-assembled into nanoparticles (IPSAM) possibly because the ion pair was amphiphilic and surface-active. The ion pair decreased in the surface activity and increased in the critical micelle concentration, when the sulfide of PTA was oxidized by H2O2. This could account for why the UCST decreased with increasing H2O2 concentration. IPSAM released its payload (i.e. nile red) in response to oxidation and temperature. Upon oxidation, the ion pair decreased in its UCST and IPSAM underwent dissolution, leading to a promoted release. Upon heating, the temperature increased above UCST, which caused IPSAM to be disassembled and release its payload. Gold nanoparticle (GNP) synthesized in situ was found to be bound to IPSAM. IPSAM bearing GNP exhibited a promoted release of its payload under near-infrared (NIR) irradiation. Heat generated by GNP would be able to disassemble IPSAM and enhance the release. Doxorubicin loaded in folated IPSAM exhibited a significant in vitro anti-cancer activity against KB cells. It could be effectively internalized into the cells, evidenced by fluorescence-activated cell sorting analysis and confocal laser scanning microscopy. When GNP was included in IPSAM, NIR irradiation led to further increase in the anti-cancer activity.