Research progress in the molecular mechanisms of histone deacetylase inhibitors for radiosensitization / 中华放射医学与防护杂志

Radiotherapy is one of the most commonly used and effective method to treat malignant tumors in clinical practice. However, there are still some limitations including high radiotherapy doses, harmful side effects on normal tissues, and radiation resistance of tumor cells. Therefore, seeking safe and effective radiotherapy sensitizers to improve radiation sensitivity of tumor cells has been focused for a long time. Histone deacetylase inhibitors (HDACIs), as a kind of epigenetic modifiers, can regulate the sensitivity of tumor cells to ionizing radiation and ultraviolet radiation in addition to the inherent anticancer characteristics. This article reviewed the molecular mechanisms of HDACIs in enhancing radiation sensitivity and by selectively killing tumor cells.

Selectively enhancing radiosensitivity of cancer cells

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity. For the first time, we used the

Preparation of ROS responsive nano prodrug and its anti-tumor activity in vitro / 天津医药

Objective To design and synthesize a novel paclitaxel loaded nanoparticle with reactive oxygen species (ROS) response, and characterize its structure, and investigate its stability, in vitro drug responsive release, cellular uptake and in vitro antitumor activity. Methods The PEG-2S-PTX monomer was synthesized by coupling the hydrophilic polyethylene glycol (PEG) with hydrophobic paclitaxel (PTX) via a thioether chain (2S), and the prodrug nanoparticles (PEG-2S-PTX NPs) were prepared by self-assembly. Meanwhile, using succinic anhydride (SA) as the linking group to synthesize the PEG-SA-PTX monomer and prepare the other prodrug nanoparticles (PEG-SA-PTX NPs) as control. The structures of PEG-2S-PTX and PEG-SA-PTX monomer were confirmed by 1H-NMR. The diameter and stability of the nanoparticles were detected by dynamic light scattering (DLS). The PTX release kinetics under oxidizing condition was detected by high performance liquid chromatography (HPLC) method. And the cellular uptake efficiency of nanoparticles by MCF-7 cells was observed by fluorescence microscope. The in vitro antitumor effects of nanoparticles were compared by MTT assay. Results PEG-2S-PTX and PEG-SA-PTX could both be self-assemble into nanoparticles with the diameter of (92.15±12.42) nm and (113.20±12.16) nm. PEG-2S-PTX NPs could rapidly release PTX under oxidative condition while PEG-SA-PTX NPs only showed weak responsiveness. PEG-2S-PTX NPs could be more rapidly taken up by MCF-7 cells compared with PEG-SA-PTX NPs. They both showed concentration dependent anti-tumor effects, but the cytotoxicity of PEG-2S-PTX NPs was stronger than that of PEG-SA-PTX NPs in the concentrations of 0.05, 0.1, 5, 10, 50 and 100 mg/L (P<0.05). Conclusion As paclitaxel prodrug nanoparticles with ROS responsive ability, PEG-2S-PTX NPs can rapidly release PTX in response to ROS in tumor cells, and exhibit great anti-tumor activity in vitro.