Kiwi-derived nanovesicles (KDNVs) as radiosensitizers and drug delivery systems for enhanced radiotherapy
Radiation therapy (RT), a standard cancer treatment, is limited by its potential to harm surrounding normal cells and resistance in cancer cells from high irradiation (IR) doses. Radiosensitizers enhance cancer cells’ response to IR but suffer from ineffective delivery mechanisms. Since many radiosensitizers are from plant extracts, this project aims to utilize plant-derived nanovesicles (PDNVs) to offer radio-sensitizing drug effects and their natural cargo-carrying abilities to deliver another radiosensitizing drug. Our previous study found that kiwi-derived nanovesicles (KDNVs) act as a radiosensitizer by inducing double-strand DNA damage. In this study, we aim to load another radiosensitizer into KDNVs to have a synergistic IR sensitizing effect to enhance tumor loss in RT. Doxorubicin (DOX), a known radiosensitizer, was chosen for its distinct activation pathway. Firstly, Dox-loading optimization in KDNVs was performed using different methods, with 45°C incubation for 4 hours being chosen. Then, the MTT assays confirmed the synergized effects of Dox-loaded KDNVs, which have more cell death than the KDNV and Dox groups. Additionally, the Clonogenic and TUNEL assay validated this synergized effect. However, assessing DNA double-strand breakages through 53BP1 and γH2AX foci numbers did not indicate this synergized effect by showing significantly higher foci number in the Dox-loaded KDNV groups after IR, which suggest an alternative pathway may be responsible for this observed synergized radio-sensitizing effect. This study showed the KDNVs as a radiosensitizer and a therapeutic carrier to load another drug for a synergistic IR effect. Further investigation is needed to determine thealternative pathway mechanisms.
