DDEL-18. PEG-AU-BP NANOCARRIERS FOR DBTRG HUMAN GLIOMA CELLS

Abstract

Abstract n-butylidenephthalide (BP) has been verified to have the superior ability of cancer cell toxicity. Furthermore, gold nanoparticles (Au) are biocompatible materials as well as the effective carrier to deliver bio-active molecular for cancer therapeutics. In present research, Au nanoparticles were firstly conjugated with polyethylene glycol (PEG), and cross-linked with BP to obtain PEG-Au-BP nanocarriers. The physicochemical properties were characterized through Ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR) and Dynamic light scattering (DLS) to confirm the combination of PEG,Au,and BP. Through iv vitro, normal BAEC cells and DBTRG human glioma cells were treated with PEG-Au-BP nanocarriers to investigate the cytotoxicity, cell uptake efficiency, and mechanism of endocytic routes. According to the results of MTT assay, PEG-Au-BP could significantly inhibit DBTRG cells proliferation. Cell uptake efficiency and potential cellular transportation in both BAEC and DBTRG cell lines were observed to be significantly higher at the time point of 2hr and 24 hr. Moreover, the mechanisms of endocytosis, clathrin-mediated endocytosis and cell autophagy, were explored to routes for BAEC and DBTRG cells to absorb PEG-Au-BP nanocarriers. Next, the cell progression and apoptosis of DBTRG cells after PEG-Au-BP treatment was investigated by flow cytometry. The results figured out that PEG-Au-BP could remarkably regulate DBTRG cell cycle at Sub-G1 phase as well as induced more apoptotic cells. The expression of apoptotic-related proteins in DBTRG cells was determined. After the treatment of PEG-Au-BP, the apoptotic cascade proteins, p21, BAX, Act-caspase-3 were significantly expressed in DBTRG cells. Through in vivo, the tissue morphology and particle distribution in mice were examined by retro-orbital sinus injection with PEG-Au-BP nanocarriers. The results demonstrated the tissue integrity in brain (forebrain, midbrain, cerebellum), and other organs did not show significant destruction. The above finding elucidated PEG-Au-BP to be a potential nanodrug for brain tumor therapies.