Critical parameters to translate gold nanoparticles as radiosensitizing agents into the clinic

Moloudi, Kave; Ali, Khaleda; Najafi, Masoud; Azmoonfar, Rasool; Azizi, Mehdi; Nekounam, Houra; Sobhani, Mahsa; Laurent, Sophie; Samadian, Hadi

doi:10.1002/wnan.1886

Cited by 11 publications

(5 citation statements)

References 141 publications

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“…This result is particularly interesting and supports the potential of this approach in improving the effectiveness of cancer therapy. Similar findings have been reported in other studies, suggesting that gold nanoparticles can function as radiosensitizers by promoting ROS generation upon exposure to X-rays 53 , 58 .…”

Section: Resultssupporting

confidence: 91%

Photothermal and radiotherapy with alginate-coated gold nanoparticles for breast cancer treatment

Ghaffarlou,

Rashidzadeh,

Mohammadi

et al. 2024

Sci Rep

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Radiation therapy and phototherapy are commonly used cancer treatments that offer advantages such as a low risk of adverse effects and the ability to target cancer cells while sparing healthy tissue. A promising strategy for cancer treatment involves using nanoparticles (NPs) in combination with radiation and photothermal therapy to target cancer cells and improve treatment efficacy. The synthesis of gold NPs (AuNPs) for use in biomedical applications has traditionally involved toxic reducing agents. Here we harnessed dopamine (DA)-conjugated alginate (Alg) for the facile and green synthesis of Au NPs (Au@Alg-DA NPs). Alg-DA conjugate reduced Au ions, simultaneously stabilized the resulting AuNPs, and prevented aggregation, resulting in particles with a narrow size distribution and improved stability. Injectable Au@Alg-DA NPs significantly promoted ROS generation in 4T1 breast cancer cells when exposed to X-rays. In addition, their administration raised the temperature under a light excitation of 808 nm, thus helping to destroy cancer cells more effectively. Importantly, no substantial cytotoxicity was detected in our Au@Alg-DA NPs. Taken together, our work provides a promising route to obtain an injectable combined radio enhancer and photothermally active nanosystem for further potential clinic translation.

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Section: Resultssupporting

confidence: 91%

Photothermal and radiotherapy with alginate-coated gold nanoparticles for breast cancer treatment

Ghaffarlou,

Rashidzadeh,

Mohammadi

et al. 2024

Sci Rep

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“…Nanotechnology brings tremendous benefits in various fields of medicine with numerous applications in diagnosis and therapy (Moloudi et al, 2023). The use of nanoparticles for the delivery of PSs has been shown to improve the efficiency of PDT and decrease its off‐target side effects (Hamblin et al, 2015).…”

Section: Nanotechnology‐mediated Pdtmentioning

confidence: 99%

Nanotechnology‐mediated photodynamic therapy: Focus on overcoming tumor hypoxia

Moloudi,

Abrahamse,

George

2023

WIREs Nanomed Nanobiotechnol

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The oxygen level in the tumor is a critical marker that determines response to different treatments. Cancerous cells can adapt to hypoxia and low pH conditions within the tumor microenvironment (TME) to regulate tumor metabolism, proliferation, and promote tumor metastasis as well as angiogenesis, consequently leading to treatment failure and recurrence. In recent years, widespread attempts have been made to overcome tumor hypoxia through different methods, such as hyperbaric oxygen therapy (HBOT), hyperthermia, O2 carriers, artificial hemoglobin, oxygen generator hydrogels, and peroxide materials. While oxygen is found to be an essential agent to improve the treatment response of photodynamic therapy (PDT) and other cancer treatment modalities, the development of hypoxia within the tumor is highly associated with PDT failure. Recently, the use of nanoparticles has been a hot topic for researchers and exploited to overcome hypoxia through Oxygen‐generating hydrogels, O2 nanocarriers, and O2‐generating nanoparticles. This review aimed to discuss the role of nanotechnology in tumor oxygenation and highlight the challenges, prospective, and recent advances in this area to improve PDT outcomes.This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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“…[3][4][5] For instance, hafnium (Hf), gold (Au), and lanthanide elements have been developed as novel radio-sensitizing nanoparticles to effectively capture more local radiation dose inside the tumor since they possess a high atomic number, thus reducing the side effects of radiation therapy. [6][7][8][9][10][11][12] During the RT, these radiosensitizers can interact with X-ray via several physical processes, releasing electrons and generating ROS, leading to irreparable DNA lesions and inducing tumor cell apoptosis. [13][14][15][16] However, the unique tumor microenvironment (TME) poses challenges to the effectiveness of radiation therapy.…”

Section: Introductionmentioning

confidence: 99%

A pH-Sensitive Nanoparticle as Reactive Oxygen Species Amplifier to Regulate Tumor Microenvironment and Potentiate Tumor Radiotherapy

Jiang,

et al. 2024

IJN

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Background: Radiotherapy is a widely used clinical tool for tumor treatment but can cause systemic toxicity if excessive radiation is administered. Although numerous nanoparticles have been developed as radiosensitizers to reduce the required dose of X-ray irradiation, they often have limitations, such as passive reliance on radiation-induced apoptosis in tumors, and little consider the unique tumor microenvironment that contributes radiotherapy resistance. Methods: In this study, we developed and characterized a novel self-assembled nanoparticle containing dysprosium ion and manganese ion (Dy/Mn-P). We systematically investigated the potential of Dy/Mn-P nanoparticles (NPs) as a reactive oxygen species (ROS) amplifier and radiosensitizer to enhance radiation therapy and modulate the tumor microenvironment at the cellular level. Additionally, we evaluated the effect of Dy/Mn-P on the stimulator of interferon genes (STING), an innate immune signaling pathway. Results: Physicochemical analysis demonstrated the prepared Dy/Mn-P NPs exhibited excellent dispersibility and stability, and degraded rapidly at lower pH values. Furthermore, Dy/Mn-P was internalized by cells and exhibited selective toxicity towards tumor cells compared to normal cells. Our findings also revealed that Dy/Mn-P NPs improved the tumor microenvironment and significantly increased ROS generation under ionizing radiation, resulting in a ~70% increase in ROS levels compared to radiation therapy alone. This enhanced ROS generation inhibited ~92% of cell clone formation and greatly contributed to cytoplasmic DNA exposure. Subsequently, the activation of the STING pathway was observed, leading to the secretion of pro-inflammatory immune factors and maturation of dendritic cells (DCs). Conclusion:Our study demonstrates that Dy/Mn-P NPs can potentiate tumor radiotherapy by improving the tumor microenvironment and increasing endogenous ROS levels within the tumor. Furthermore, Dy/Mn-P can amplify the activation of the STING pathway during radiotherapy, thereby triggering an anti-tumor immune response. This novel approach has the potential to expand the application of radiotherapy in tumor treatment.

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Critical parameters to translate gold nanoparticles as radiosensitizing agents into the clinic

Cited by 11 publications

References 141 publications

Photothermal and radiotherapy with alginate-coated gold nanoparticles for breast cancer treatment

Photothermal and radiotherapy with alginate-coated gold nanoparticles for breast cancer treatment

Nanotechnology‐mediated photodynamic therapy: Focus on overcoming tumor hypoxia

A pH-Sensitive Nanoparticle as Reactive Oxygen Species Amplifier to Regulate Tumor Microenvironment and Potentiate Tumor Radiotherapy

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