Mesoporous Silica Nanoparticles for Combined Delivery of Polo-Like Kinase 1 (PLK1) and Epidermal Growth Factor Receptor (EGFR) Inhibitors Enhances Radio Sensibility in Non-Small Cell Lung Cancer

Abstract

The aim of this study was to clarify the role of nanoparticle for combined delivery of polo-like kinase 1 (PLK1) and EGFR inhibitors in non-small cell lung cancer progress in vitro and its effect on radio sensibility. Mesoporous silica nanoparticles (MSNP) that targeted EGFR (epidermal growth factor receptor) were established and loaded with PLK1 siRNA. Apoptosis and cell cycle with different treatments were analyzed by flow cytometry. Cell proliferation and cell viability were tested by cloning and CCK-8 assay. We employed PCR and Westernblot to detect PLK1 transcription and protein expression. Finally, a tumor metastasis model was established. EGFR+ NSCLC cell lines exhibited notable increase in C-siPLK1-NP phagocytosis and more powerful suppression in EFGR level. Further, C-siPLK1-NP exposure resulted in notable reduced PLK1 mRNA and protein level, accompanied by prominent limited cell vitality, blocked cell cycle at G2/M. With radiation, C-siPLK1-NP exposure induced enhanced radio sensibility, as proved by remarkable reduced cloning efficiency, fraction surviving and evident increase in γH2ax foci. Finally, mice that were administered with C-siPLK1-NP exerted more obvious tumor progression. Nanoparticles’ combined delivery of PLK1 and EGFR inhibitors inhibited NSLCC cell proliferation, induced apoptosis, and enhanced radiosensitivity in vitro and in vivo.