Metronidazole-modified Au@BSA nanocomposites for dual sensitization of radiotherapy in solid tumors.

ABSTRACT

The hypoxic microenvironment of solid tumors can lead to reduced therapeutic DNA damage to the tumor cells, thus diminishing tumor sensitivity to radiotherapy. Although hypoxic radiosensitizers can improve radiotherapy efficacy by enhancing the role of oxygen, their effects are limited by the uneven distribution of oxygen within solid tumor tissues. In this study, a novel radiosensitizer via leveraging gold complexes and metronidazole (MN) was synthesized to improve radiotherapeutic efficacy. The gold atoms incorporated in the radiosensitizer enabled efficient deposition of high-energy radiation; the hydrophobic metronidazole was reduced to hydrophilic aminoimidazole under hypoxia conditions and further promoted radiotherapy sensitization. The results of CCK-8 assays, Live/Dead assays, γ-H2AX immunofluorescence indicated that metronidazole-modified Au@BSA nanocomposites (NCs) exhibited excellent antitumor effects. The in vivo antitumor tests further showed an inhibition rate of 100%. These results demonstrated that the NCs successfully enhanced radiotherapy efficacy by the dual sensitization strategy. Overall, we believe this multimodal radiosensitizing nanocomplex can significantly inhibit tumor growth and metastasis, with their hypoxia-oriented characteristics ensuring a higher efficacy and safety.