Abstract
Paclitaxel (Ptx) is widely utilized to treat liver cancer, and the treatment benefit of reactive oxygen species (ROS)-responsive Ptx nanoprodrug is investigated in this study. The one-step nano-precipitation method was utilized to self-assembly DSPE-PEG2000 -thioketal linker (TK)-Ptx with pyropheophorbide acid nanoparticles (PPa NPs) to form PPa/Ptx NPs. Dynamic light scattering and transmission electron microscopy were used for characterization, and 2'-7'dichlorofluorescin diacetate staining was utilized for intracellular ROS detection. HepG2 cells viability and tumor growth rate of HepG2 bearing mice were assayed. Hematoxylin and eosin staining, proliferating cell nuclear antigen detection, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay were utilized for histology assessment. PPa/Ptx NPs incubation with light irradiation showed superior cytotoxicity to HepG2 cells with increased intracellular ROS production than PPa/Ptx NPs incubation without light irradiation or PPa NPs incubation with light irradiation. At the same time, PPa/Ptx NPs with light irradiation could significantly decrease the tumor growth in vivo as indicated by diminished tumor volume with the largest necrotic area, the highest rate of apoptotic cells, and the least proliferating cells. PPa/Ptx NPs show synergistic chemo-photodynamic characteristics, which could be considered as a promising treatment option for liver cancer.
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