Gold Nanoparticle-Enhanced and Size-Dependent Generation of Reactive Oxygen Species from Protoporphyrin IX

Photosensitizer, protoporphyrin IX (PpIX), was conjugated with Au nanoparticles (Au NPs) of 19, 66, and 106 nm diameter to study the size-dependent enhancement of reactive oxygen species (ROS) formation enabled by Au NPs. The ROS enhancement ratio is determined to be 1:2.56:4.72 in order of increasing Au NP size, in general agreement with theoretically calculated field enhancement to the fourth power. The convergence of the experimental and simulated results suggests that Au NP-enhanced and size-dependent ROS formation can be attributed directly to the localized electromagnetic field as a result of surface plasmonic resonance of Au NPs under light irradiation. In vitro study on the ROS formation enabled by PpIX-conjugated Au NPs in human breast cancer cells (MDA-MB-231) revealed the similar size-dependent enhancement of intracellular ROS formation, while the enhancement greatly depended on cellular uptake of Au NPs. Cellular photodynamic therapy revealed that cell destruction significantly increased in the presence of Au NPs. Compared to the untreated control (0% destruction), 22.6% cell destruction was seen in the PpIX alone group and more than 50% cell destruction was obtained for all PpIX-conjugated Au NPs. The 66 nm Au NPs yielded the highest cell destruction, consistent with the highest cellular uptake and highest ROS formation. Clearly, the complex cellular environment, size-dependent cellular uptake of Au NPs, and ROS generations are vital contributors to the overall cellular PDT efficacy.