The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation

Liu, Xi; Liu, Yan; Zhang, Pengcheng; Jin, Xiaodong; Zheng, Xiaogang; Ye, Fei; Chen, Weiqiang; Li, Qiang

doi:10.2147/ijn.s105348

Cited by 31 publications

(25 citation statements)

References 40 publications

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“…We found that AuNPs could significantly improve the hydroxyl radical production and the cell-killing effects of X-rays and fast carbon ions 12 . We also synthesized the reductive thioctyl tirapazamine (TPZs)-modified AuNPs (TPZs-AuNPs) and showed their ability for radiation enhancement 24 . We further proposed that ionizing radiation exposure was cell cycle phase-dependent for cellular uptake of gold nanoclusters (AuNCs).…”

Section: Metal-based Nanoenhancers For Ionizing Ramentioning

confidence: 99%

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

et al. 2018

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Radiotherapy is one of the major therapeutic strategies for cancer treatment. In the past decade, there has been growing interest in using high Z (atomic number) elements (materials) as radiosensitizers. New strategies in nanomedicine could help to improve cancer diagnosis and therapy at cellular and molecular levels. Metal-based nanoparticles usually exhibit chemical inertness in cellular and subcellular systems and may play a role in radiosensitization and synergistic cell-killing effects for radiation therapy. This review summarizes the efficacy of metal-based NanoEnhancers against cancers in both in vitro and in vivo systems for a range of ionizing radiations including gamma-rays, X-rays, and charged particles. The potential of translating preclinical studies on metal-based nanoparticles-enhanced radiation therapy into clinical practice is also discussed using examples of several metal-based NanoEnhancers (such as CYT-6091, AGuIX, and NBTXR3). Also, a few general examples of theranostic multimetallic nanocomposites are presented, and the related biological mechanisms are discussed.

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Section: Metal-based Nanoenhancers For Ionizing Ramentioning

confidence: 99%

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

et al. 2018

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“…Our work has focused on the biological mechanisms of ionizing radiation, including the radiosensitizing mechanisms of nanoparticles. [23][24][25] The aim of the present study was to evaluate the radiosensitizing effects and mechanism of GONs in NSCLC cells under X-ray irradiation. After the cellular uptake and cell viability of GONs in NSCLC cells were studied, the clonogenic survival fractions of human NSCLC cells were investigated in the presence of GONs under X-ray irradiation compared to that of cells treated with irradiation alone.…”

Section: Introductionmentioning

confidence: 99%

<p>Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy</p>

Li¹,

Li²,

Jiang³

et al. 2019

IJN

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Background Gadolinium-based nanoparticles (GdNPs) have been used as theranostic sensitizers in clinical radiotherapy studies; however, the biomechanisms underlying the radio-sensitizing effects of GdNPs have yet to be determined. In this study, ultra-small gadolinium oxide nanocrystals (GONs) were employed to investigate their radiosensitizing effects and biological mechanisms in non-small-cell lung cancer (NSCLC) cells under X-ray irradiation. Method and materials GONs were synthesized using polyol method. Hydroxyl radical production, oxidative stress, and clonogenic survival after X-ray irradiation were used to evaluate the radiosensitizing effects of GONs. DNA double-strand breakage, cell cycle phase, and apoptosis and autophagy incidences were investigated in vitro to determine the radiosensitizing biomechanism of GONs under X-ray irradiation. Results GONs induced hydroxyl radical production and oxidative stress in a dose- and concentration-dependent manner in NSCLC cells after X-ray irradiation. The sensitizer enhancement ratios of GONs ranged between 19.3% and 26.3% for the NSCLC cells under investigation with a 10% survival rate compared with that of the cells treated with irradiation alone. Addition of 3-methyladenine to the cell medium decreased the incidence rate of autophagy and increased cell survival, supporting the idea that the GONs promoted cytostatic autophagy in NSCLC cells under X-ray irradiation. Conclusion This study examined the biological mechanisms underlying the radiosensitizing effects of GONs on NSCLC cells and presented the first evidence for the radiosensitizing effects of GONs via activation of cytostatic autophagy pathway following X-ray irradiation.

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“…Contrary to previous reports, in which similar TPZ–amide analogs were formed, we found that traditional carbodiimide‐ or uronium‐based coupling approaches produced numerous unidentified side products, which were impossible to remove with column chromatography . Alternatively, the use of acid anhydrides alone was not powerful enough to allow a reaction to take place.…”

Section: Resultsmentioning

confidence: 99%

Macrophage‐Mediated Delivery of Hypoxia‐Activated Prodrug Nanoparticles

Evans

Shields

Krishnan

et al. 2019

Advanced Therapeutics

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Hypoxia‐activated prodrugs (HAPs) have tremendous clinical potential due to their selective toxicity toward poorly oxygenated tissues, which is a hallmark of solid tumors. Despite their promising results in vitro, HAPs have failed to make a clinical impact. This is largely because tumor hypoxia is located far from blood vessels, making it difficult for HAPs to accumulate in therapeutically sufficient concentrations. Here, a generalized strategy to overcome this barrier by employing macrophages as drug carriers to enhance the penetration and accumulation of HAPs deep in solid tumors is reported. The system leverages the chemotactic and phagocytic abilities of macrophages to improve delivery of nanoparticles encapsulating a model HAP, tirapazamine (TPZ), to the hypoxic regions of solid tumors. A sequence of in vitro assays is used to refine the properties of the system by minimizing carrier cell toxicity while maximizing therapeutic efficacy. It is demonstrated in vivo that the system improves drug accumulation in hypoxic areas of 4T1 breast tumors and slows their growth by itself and in combination with irinotecan. The results provide early evidence that macrophages can significantly improve the transport and efficacy of HAPs by improving their tumor penetration, highlighting a potential strategy to advance them into the clinic.

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The synergistic radiosensitizing effect of tirapazamine-conjugated gold nanoparticles on human hepatoma HepG2 cells under X-ray irradiation

Cited by 31 publications

References 40 publications

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

Metal-based NanoEnhancers for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

<p>Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy</p>

Macrophage‐Mediated Delivery of Hypoxia‐Activated Prodrug Nanoparticles

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