Fabrication of nanohybrids toward improving therapeutic potential of a NIR photo-sensitizer: An optical spectroscopic and computational study

Abstract

Implementation of near infrared radiation (NIR) active drugs in photodynamic therapy (PDT) is considered as a highly promising tool in therapeutic application. Because of its strong NIR absorbance, indocyanine green (ICG) has become an attractive choice in emerging photo-theranostics. ICG generates singlet oxygen as well as shows photothermal effect under NIR irradiation. However, ICG is unable to produce sufficient amount of others types of reactive oxygen species (ROS) such as superoxide, hydroxyl radical. But, its ability of singlet oxygen generation under NIR irradiation is arrested by its tendency to aggregate in aqueous medium. Because of this limitation, it shows better effectiveness in photothermal therapy compare to it’s action as a photodynamic agent. Herein, we have addressed to overcome this limitation via the fabrication of zinc oxide (ZnO) based ICG-ZnO nanohybrid which provides lesser H-aggregation between ICG molecules on its surface and yield significantly greater amount of ROS relative to ICG upon photoexcitation, due to excited state electron transfer from ICG to ZnO. Also, this surface functionalization prevents aggregation of ICG in water significantly. Classical MD simulation shows the dimeric structure of ICG breakes down on ZnO surface which corroborates results from the aggregation study in water. Density functional theory (DFT) along with time-dependent DFT studies elucidate that upon photoexcitation electron transfer takes place from the higher energy orbital of ICG to the conduction band of ZnO. The greater efficiency in ROS generation by the ICG-ZnO nanohybrid than ICG or ZnO demonstrates remarkable antimicrobial activity against gram-negative bacteria E. coli. Overall, the present study highlights the scope of developing ICG-ZnO nanohybrid as a highly efficient NIR agent for use in antibacterial photodynamic therapy.