P-Y/G@NHs sensitizes non-small cell lung cancer cells to radiotherapy via blockage of the PI3K/AKT signaling pathway

Radioresistance represents a common phenomenon found in Cancer treatment. Herein, the current study sought to evaluate the effects of a nanodrug delivery system of YSAYPDSVPMMS (YSA) peptide-modified gold nanoparticles-dextran-based hydrogel loaded with paclitaxel-succinic anhydride (P-Y/G@NHs) on non-small cell lung Cancer (NSCLC) cell radiosensitivity. Firstly, utilizing the coupling reaction and layer-by-layer assembly technique, P-Y/G@NHs was prepared. The therapeutic effects of the P-Y/G@NHs in NSCLC cells in relation to the PI3K/Akt signaling pathway were examined by assessing the colony formation, Apoptosis, and Reactive Oxygen Species (ROS) generation of A549 cells under 10 Gy X-rays irradiation. Moreover, A549 tumor-bearing mice were generated to further validate the therapeutic effect in vivo. We confirmed the successful conjugation of the nanocomposite. Under 10 Gy X-rays irradiation, P-Y/G@NHs reduced the number of colonies of A549 cells, while inducing both cell Apoptosis and ROS production. Moreover, P-Y/G@NHs enhanced the radiosensitivity of A549 cells by inhibiting the PI3K/Akt signaling pathway. In vivo fluorescence experiments validated that P-Y/G@NHs effectively-targeted and accumulated at the tumor site in nude mice, thus augmenting the radiosensitivity of tumors without significant immune toxicity or side effects. Conclusively, our findings highlighted that P-Y/G@NHs significantly enhanced the radiosensitivity of NSCLC cells by repressing the PI3K/Akt signaling pathway.

Biocompatibility; Biosafety; Dextran; Gold nanoparticles; Non-small cell lung cancer; PI3K/AKT signaling pathway; Paclitaxel; Radiosensitivity; YSA peptide.