Self-assembled gold nanostar-NaYF₄:Yb/Er clusters for multimodal imaging, photothermal and photodynamic therapy

A grand challenge for medicine is to develop tools to selectively image and treat diseased cells. Rare earth doped upconverting nanoparticles (UCNPs) have been extensively studied for imaging applications because of their ability to absorb near infrared radiation (NIR) and emit visible light, but these particles cannot induce therapy alone. Recently, we developed methods to couple the UCNPs to visible and NIR-absorbing gold nanostructures through nucleic acid interactions. Here, we show that gold-UCNP clusters with optimized plasmon resonance and particle compositions provide both in vitro imaging contrast and combination cell killing through simultaneous photothermal (PTT) and photodynamic (PDT) therapy. PDT was induced by embedding singlet oxygen photosensitizers in silica shells on the UCNPs. Upon photoexcitation with 980 nm light, the NIR absorbing gold-UCNP clusters both increased the local temperature and generated singlet oxygen, increasing cell killing relative to either modality alone. The multifunctional polyethylene glycol (PEG) coated gold-NaYF₄:Yb/Er clusters exhibited high biocompatibility without irradiation but synergistic cell killing of MCF-7 cancer cells under light excitation. Finally, we also demonstrate that an optimal gold plasmon resonance is critical for minimizing absorbance overlap with the photosensitizers.