Pro-Oxidant Drug-Loaded Au/ZnO Hybrid Nanoparticles for Cancer-Specific Chemo-Photodynamic Combination Therapy.
Eun Ji HongPadmanaban SivakumarVasanthan RavichandranDae Gun ChoiYoon-Seok KimMin Suk ShimPublished in: ACS biomaterials science & engineering (2019)
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.
Keyphrases
- reduced graphene oxide
- drug delivery
- combination therapy
- cancer therapy
- visible light
- room temperature
- quantum dots
- photodynamic therapy
- reactive oxygen species
- sensitive detection
- gold nanoparticles
- papillary thyroid
- cell death
- breast cancer cells
- light emitting
- dna damage
- squamous cell
- emergency department
- cell cycle arrest
- oxidative stress
- working memory
- risk assessment
- climate change
- radiation therapy
- endothelial cells
- childhood cancer
- energy transfer
- cell proliferation
- pluripotent stem cells