Abstract
Gadolinium-based nanomaterials can not only serve as contrast agents but also contribute to sensitization in the radiotherapy of cancers. Among radiotherapies, carbon ion irradiation is considered one of the superior approaches with unique physical and biological advantages. However, only a few metallic nanoparticles have been used to improve carbon ion irradiation. In this study, gadolinium oxide nanocrystals (GONs) were synthesized using a polyol method to decipher the radiosensitizing mechanisms in non-small cell lung cancer (NSCLC) cell lines irradiated by carbon ions. The sensitizer enhancement ratio at the 10% survival level was correlated with the concentration of Gd in NSCLC cells. GONs elicited an increase in hydroxyl radical production in a concentration-dependent manner, and the yield of reactive oxygen species increased obviously in irradiated cells, which led to DNA damage and cell cycle arrest. Apoptosis and cytostatic autophagy were also significantly induced by GONs under carbon ion irradiation. The GONs may serve as an effective theranostic material in carbon ion radiotherapy for NSCLC.Graphical
Highlights
Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 18.4% of the total cancer-related deaths per year and 11.6% of the newly diagnosed cases [1]
We examined cellular reactive oxygen species (ROS) production, DNA double-strand breakage (DSB), and cell cycle distribution as well as apoptosis and autophagy induction to unravel the potential mechanisms of the radiosensitizing effect of gadolinium oxide nanocrystals (GONs) in NSCLC cells under carbon ion irradiation
We examined the radiation enhancement ratio of GONs on hydroxyl radical production in aqueous solution under carbon ion irradiation using 3-coumarin carboxylic acid (3-CCA) as a probe following the reported procedure [11]
Summary
Non-small cell lung cancer (NSCLC) is the most common lung cancer, accounting for approximately 18.4% of the total cancer-related deaths per year and 11.6% of the newly diagnosed cases [1]. NSCLC patients are always diagnosed at an advanced phase or with metastasis and are ineligible for surgery and have a poor prognosis; namely, the 5-year survival rate is only 16.1% [2]. Aside from surgery and chemotherapy, radiation therapy is an effective treatment, especially for patients with locally or regionally advanced NSCLC [3]. The use of carbon ions contributes to a higher probability of damage to tumors as well as a lower risk to surrounding health tissue than does conventional radiotherapy [4]. Compared to X-rays, carbon ion irradiation possesses the potential advantages including a better physical dose distribution, a greater reduction in lateral scattering [5], higher relative biological effectiveness (RBE), and a lower oxygen enhancement ratio (OER), all of which are desirable features for killing radioresistant, hypoxic tumors [6]. Carbon ion therapy is considered one of the superior noninvasive approaches for the treatment of tumors located in highly sensitive tissues such as lung and for tumors that are resistant to
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