Upconversion nanoparticles conjugated with curcumin as a photosensitizer to inhibit methicillin-resistant Staphylococcus aureus in lung under near infrared light

Abstract

Yong Ye, Yue Li, Fei FangDepartment of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, People’s Republic of ChinaAbstract: Curcumin has phototoxic effects on bacteria under <450 nm irradiation, but it is unstable in vivo and cannot exert effects on deep tissues. Near infrared light (NIR) is harmless to the body and has stronger penetration than visible light. In order to improve the effects of curcumin, upconversion nanoparticles conjugated with curcumin (UCNPs-curcumin) are designed to upconvert NIR to the excitation wavelength of curcumin. UCNPs-curcumin were synthesized using polyethyleneimine to combine curcumin and UCNPs, based on typical composition of lanthanide nitrates Re(NO)3 (Y:Yb:Er=78%:20%:2%) linked by ethylenediaminetetraacetic acid in sodium fluoride (NaF) matrix, to upconvert NIR to 432 nm light. The product was characterized by size distribution, thermogravimetric analysis, differential scanning calorimetry, and scanning electron microscopy. Growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA) was not only measured in vitro but also investigated on MRSA-induced pneumonia in mice. The results showed that curcumin was covered by UCNPs to form stable nanoparticles whose average size was 179.5 nm and zeta potential was -33.7 mV in normal saline. The UCNPs-curcumin produced singlet oxygen, which reaches a stable level after 30 minutes of irradiation, and took effect on MRSA through bacterial cytoplasm leakage. They alleviated MRSA-induced pneumonia and reduced bacterial counts in lungs with 980 nm irradiation (0.5 W/cm2) on chests of mice. It is confirmed that the UCNPs-curcumin in lungs are activated under NIR irradiation and strengthen their antibacterial effects on MRSA. This research provides a new type of NIR photosensitizer, which plays an important role in phototoxic effects of curcumin in deep tissues under NIR. Keywords: curcumin, upconversion nanoparticle, near infrared light, methicillin-resistant Staphylococcus aureus, phototoxicity