scholarly journals Intracellular Delivery of Doxorubicin by Iron Oxide-Based Nano-Constructs Increases Clonogenic Inactivation of Ionizing Radiation in HeLa Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 6778
Author(s):  
Roxana Cristina Popescu ◽  
Diana Iulia Savu ◽  
Miriam Bierbaum ◽  
Adriana Grbenicek ◽  
Frank Schneider ◽  
...  

In this study, we determined the potential of polyethylene glycol-encapsulated iron oxide nanoparticles (IONPCO) for the intracellular delivery of the chemotherapeutic doxorubicin (IONPDOX) to enhance the cytotoxic effects of ionizing radiation. The biological effects of IONP and X-ray irradiation (50 kV and 6 MV) were determined in HeLa cells using the colony formation assay (CFA) and detection of γH2AX foci. Data are presented as mean ± SEM. IONP were efficiently internalized by HeLa cells. IONPCO radiomodulating effect was dependent on nanoparticle concentration and photon energy. IONPCO did not radiosensitize HeLa cells with 6 MV X-rays, yet moderately enhanced cellular radiosensitivity to 50 kV X-rays (DMFSF0.1 = 1.13 ± 0.05 (p = 0.01)). IONPDOX did enhance the cytotoxicity of 6 MV X-rays (DMFSF0.1 = 1.3 ± 0.1; p = 0.0005). IONP treatment significantly increased γH2AX foci induction without irradiation. Treatment of HeLa cells with IONPCO resulted in a radiosensitizing effect for low-energy X-rays, while exposure to IONPDOX induced radiosensitization compared to IONPCO in cells irradiated with 6 MV X-rays. The effect did not correlate with the induction of γH2AX foci. Given these results, IONP are promising candidates for the controlled delivery of DOX to enhance the cytotoxic effects of ionizing radiation.

This chapter describes the interactions of X-rays with matter, the biological effects of ionizing radiation (including estimated dose thresholds), the science behind radiation dosimetry, and principles of protection of people and the environment. It goes on to describe patient dose according to scanner design, scan parameters, and methods to manage and optimize radiation doses.


Open Biology ◽  
2015 ◽  
Vol 5 (4) ◽  
pp. 150011 ◽  
Author(s):  
Ewa Markiewicz ◽  
Stephen Barnard ◽  
Jackie Haines ◽  
Margaret Coster ◽  
Orry van Geel ◽  
...  

Elevated cataract risk after radiation exposure was established soon after the discovery of X-rays in 1895. Today, increased cataract incidence among medical imaging practitioners and after nuclear incidents has highlighted how little is still understood about the biological responses of the lens to low-dose ionizing radiation (IR). Here, we show for the first time that in mice, lens epithelial cells (LECs) in the peripheral region repair DNA double strand breaks (DSB) after exposure to 20 and 100 mGy more slowly compared with circulating blood lymphocytes, as demonstrated by counts of γH2AX foci in cell nuclei. LECs in the central region repaired DSBs faster than either LECs in the lens periphery or lymphocytes. Although DSB markers (γH2AX, 53BP1 and RAD51) in both lens regions showed linear dose responses at the 1 h timepoint, nonlinear responses were observed in lenses for EdU (5-ethynyl-2′-deoxy-uridine) incorporation, cyclin D1 staining and cell density after 24 h at 100 and 250 mGy. After 10 months, the lens aspect ratio was also altered, an indicator of the consequences of the altered cell proliferation and cell density changes. A best-fit model demonstrated a dose-response peak at 500 mGy. These data identify specific nonlinear biological responses to low (less than 1000 mGy) dose IR-induced DNA damage in the lens epithelium.


2020 ◽  
Vol 21 (23) ◽  
pp. 9304
Author(s):  
Xunwen Xue ◽  
Yasser F. Ali ◽  
Caorui Liu ◽  
Zhiqiang Hong ◽  
Wanrong Luo ◽  
...  

With the advent of long-duration space explorations, ionizing radiation (IR) may pose a constant threat to astronauts without the protection of Earth’s magnetic field, or hypomagnetic field (HMF). However, the potential biological effects of a HMF on the cellular response to IR have not been well characterized so far. In this study, immortalized human bronchial epithelial cells were exposed to X-rays under either a geomagnetic field (GMF, ~50 uT) or HMF (<50 nT) culture condition. A significant increase of the cell survival rate in HMF after radiation was observed by colony formation analysis. The kinetics of DNA double-strand breaks (DSBs), determined by γH2AX foci formation and disappearance, presented a faster decrease of foci-positive cells and a significantly lower mean number of γH2AX foci per nucleus in HMF-cultured cells than in GMF-cultured cells after radiation. In addition, a γH2AX/53BP1 colocalization assay showed an upregulated DSB recovery rate in HMF cultured cells. These findings provided the first evidence that HMF exposure may enhance the cellular DSB repair efficiency upon radiation, and consequently modulate the genotoxic effects of IR.


2014 ◽  
Vol 48 (2) ◽  
pp. 142-154 ◽  
Author(s):  
Zhitong Bing ◽  
Guanghui Yang ◽  
Yanan Zhang ◽  
Fengling Wang ◽  
Caiyong Ye ◽  
...  

Abstract Background. Carbon ion therapy may be better against cancer than the effects of a photon beam. To investigate a biological advantage of carbon ion beam over X-rays, the radioresistant cell line HeLa cells were used. Radiationinduced changes in the biological processes were investigated post-irradiation at 1 h by a clinically relevant radiation dose (2 Gy X-ray and 2 Gy carbon beam). The differential expression proteins were collected for analysing biological effects. Materials and methods. The radioresistant cell line Hela cells were used. In our study, the stable isotope labelling with amino acids (SILAC) method coupled with 2D-LC-LTQ Orbitrap mass spectrometry was applied to identity and quantify the differentially expressed proteins after irradiation. The Western blotting experiment was used to validate the data. Results. A total of 123 and 155 significantly changed proteins were evaluated with treatment of 2 Gy carbon and X-rays after radiation 1 h, respectively. These deregulated proteins were found to be mainly involved in several kinds of metabolism processes through Gene Ontology (GO) enrichment analysis. The two groups perform different response to different types of irradiation. Conclusions. The radioresistance of the cancer cells treated with 2 Gy X-rays irradiation may be largely due to glycolysis enhancement, while the greater killing effect of 2 Gy carbon may be due to unchanged glycolysis and decreased amino acid metabolism.


Author(s):  
Giovanni Alcocer ◽  
Priscilla Alcocer ◽  
Carlos Marquez

Abstract This article consists of the study and investigative analysis of the effects of burns by radiation in humans. Cases of nuclear accidents, such as Chernobyl (ionizing radiation) and the effects of non-ionizing radiation such as infrared and microwave radiation are detailed. It is examined cases of injuries and burns by ionizing radiation due to irradiation (diagnostic equipment and medical treatment: X-rays, radiotherapy) or contamination (nuclear accidents, wars). Injuries and burns are also caused by nonionizing radiation, such as visible light (laser), ultraviolet, radiofrequency. There are numerous biological issues in the case of tissues, the ionizing radiation (ionizing particles and electromagnetic radiation: X-rays, gamma rays and high energy ultraviolet) can cause damage mainly in the DNA. This can cause mutations in its genetic code and cancer 5. In addition, damage to other tissues and organs can occur, as well as burns, erythema and lesions. The biological effects of nonionizing radiation are currently under investigation. Burns, erythema and lesions can also occur due to the following types of radiation: low energy ultraviolet, visible light, infrared, microwave, radiofrequency, electromagnetic fields. The purpose of this article is to provide an exhaustive analysis of all types of both ionizing and non-ionizing radiation and their effects on living beings. Finally, it is important to follow all safety and radiation protections against both ionizing and non-ionizing radiation.


2020 ◽  
Vol 21 (19) ◽  
pp. 7220
Author(s):  
Roxana Cristina Popescu ◽  
Mihai Straticiuc ◽  
Cosmin Mustăciosu ◽  
Mihaela Temelie ◽  
Roxana Trușcă ◽  
...  

This study aims to investigate whether ionizing radiation combined with doxorubicin-conjugated iron oxide nanoparticles (NP-DOX) improves the internalization and cytotoxic effects of the nano-carrier-mediated drug delivery in MG-63 human osteosarcoma cells. NP-DOX was designed and synthesized using the co-precipitation method. Highly stable and crystalline nanoparticles conjugated with DOX were internalized in MG-63 cells through macropinocytosis and located in the perinuclear area. Higher nanoparticles internalization in MG-63 cells previously exposed to 1 Gy X-rays was correlated with an early accumulation of cells in G2/M, starting at 12 h after treatment. After 48 h, the application of the combined treatment led to higher cytotoxic effects compared to the individual treatment, with a reduction in the metabolic capacity and unrepaired DNA breaks, whilst a low percent of arrested cells, contributing to the commitment of mitotic catastrophe. NP-DOX showed hemocompatibility and no systemic cytotoxicity, nor histopathological alteration of the main organs.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
R. C. Popescu ◽  
D. Savu ◽  
I. Dorobantu ◽  
B. S. Vasile ◽  
H. Hosser ◽  
...  

Nanomedicine ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. 925-941
Author(s):  
Senem Çitoğlu ◽  
Özlem Duyar Coşkun ◽  
Le Duc Tung ◽  
Mehmet Ali Onur ◽  
Nguyen Thi Kim Thanh

Aim: Superparamagnetic cubic iron oxide nanoparticles (IONPs) were synthesized and functionalized with meso-2,3-dimercaptosuccinic acid (DMSA) as a potential agent for cancer treatment. Methods: Monodisperse cubic IONPs with a high value of saturation magnetization were synthesized by thermal decomposition method and functionalized with DMSA via ligand exchange reaction, and their cytotoxic effects on HeLa cells were investigated. Results: DMSA functionalized cubic IONPs with an edge length of 24.5 ± 1.9 nm had a specific absorption rate value of 197.4 W/gFe (15.95 kA/m and 488 kHz) and showed slight cytotoxicity on HeLa cells when incubated with 3.3 × 1010, 6.6 × 1010 and 9.9 × 1010 NP/mL for 24, 48 and 72 h. Conclusion: To the best of our knowledge, this is the first study to investigate both the cytotoxic effects of DMSA-coated cubic IONPs on HeLa cells and hyperthermia performance of these nanoparticles.


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