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Gold nanoparticle (Au NP)@ZnO nanorod (NR) (Au@ZnO) hybrids with various ZnO: Au molar ratios were developed to enhance the generation of reactive oxygen species (ROS) in photodynamic therapy (PDT) applications. Introducing a metal/semiconductor heterostructure interface between Au NPs and ZnO NRs modulated electron transfer under ultraviolet (UV) irradiation, which dramatically suppressed the electron-hole recombination in ZnO and simultaneously increased the amount of excited electrons with high energy at Au NP surfaces. Hence, the ROS yield of the nanohybrid was considerably improved over those of pristine Au NPs or ZnO NRs alone and demonstrated a "1 + 1 > 2 effect." This enhancement was strengthened with increases in the proportion of Au in the hybrid. The results showed that the Au@ZnO nanohybrids with a ZnO: Au ratio of 20:1 generated the highest ROS yield because they had the largest interface area between Au and ZnO, which in turn led to the lowest cell viability for HeLa and C2C12 cells during PDT. Furthermore, both ROS generation and cell destruction were positively correlated with nanohybrid dosage. The Au@ZnO hybrid (20:1, 100 μg/mL) resulted in HeLa cell viability as low as 28% after UV exposure for 2 min, which indicated its promising potential to improve the therapeutic efficacy of PDT.
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