Pro-Oxidant Drug-Loaded Au/ZnO Hybrid Nanoparticles for Cancer-Specific Chemo-Photodynamic Combination Therapy

• Published in: ACS biomaterials science & engineering Vol. 5; no. 10; pp. 5209 - 5217
• Main Authors: Hong, Eun Ji, Sivakumar, Padmanaban, Ravichandran, Vasanthan, Choi, Dae Gun, Kim, Yoon-Seok, Shim, Min Suk
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 14-10-2019
• Subjects: cancer therapy; piperlongumine; zinc oxide nanoparticles; photodynamic therapy
• ISSN: 2373-9878; 2373-9878
• DOI: 10.1021/acsbiomaterials.9b01339

Photodynamic therapy (PDT) is a noninvasive therapeutic strategy involving photosensitizers and external light for the selective destruction of target tumors. Chemo-photodynamic combination therapy has attracted widespread attention to improve the outcome of cancer treatment by PDT only. In this study, light-triggered reactive oxygen species (ROS)-generating, polyethylene glycol (PEG)-coated zinc oxide nanorods (PEG-ZnO NRs) were synthesized and complexed with pro-oxidant piperlongumine (PL) to achieve cancer-targeted chemo-photodynamic combination therapy. It was found that PEG-ZnO NRs considerably increased intracellular ROS under UV light irradiation. The loading of PL to PEG-ZnO NRs further increased the intracellular ROS levels in MCF-7 human breast cancer cells due to efficient intracellular delivery of PL. As a result, PL-loaded PEG-ZnO NRs (PL-PEG-ZnO NRs) exhibited a synergistic anticancer activity under UV irradiation compared to free PL and PEG-ZnO NRs. PEG-ZnO NRs were further modified with Au NPs to enhance their capability of generating ROS under light. Au NP-coated PEG-ZnO NRs (Au/PEG-ZnO NRs) with UV irradiation showed higher ROS quantum yields as compared to PEG-ZnO NRs. As a result, PL-loaded Au/PEG-ZnO NRs (PL-Au/PEG-ZnO NRs) exhibited higher cytotoxicity than PL-PEG-ZnO NRs upon UV irradiation. Moreover, PL-Au/PEG-ZnO NRs showed cancer-specific cytotoxicity in MCF-7 cells due to the cancer-specific apoptosis induced by pro-oxidant PL. This study demonstrates that PL-Au/PEG-ZnO NRs have high potential for efficient and cancer-targeted chemo-photodynamic combination therapy.