Metal-based <i>NanoEnhancers</i> for Future Radiotherapy: Radiosensitizing and Synergistic Effects on Tumor Cells

Liu, Yan; Zhang, Pengcheng; Li, Feifei; Jin, Xiaodong; Jin, Li; Chen, Weiqiang; Li, Qiang

doi:10.7150/thno.22172

Cited by 257 publications

(207 citation statements)

References 295 publications

(288 reference statements)

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“…), and high‐Z elements (e.g., Au, Ba, Bi, Pt, W, etc.) . The gasotransmitters can mimic the radiosensitizing effect of oxygen and downregulate hypoxia‐inducible factor‐1 alpha (HIF‐1α) expression, while anticancer drugs can induce cancer cells to enter the G2/M phase which is the most radiation‐sensitive cell‐cycle phase .…”

Section: Introductionmentioning

confidence: 99%

Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics

et al. 2019

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treat cancer patients; however, it can cause severe systemic toxicity and immunesystem depression due to its nonspecific nature. [2][3][4] As a noninvasive therapeutic modality, radiotherapy (RT) with assistance from image guidance/positioning can be used to deliver X/γ-ray radiation to tumors. [5][6][7][8] This enables radiation oncologists to target malignant tissues for precise cancer therapy [9][10][11] while minimizing radiation dose delivered to surrounding normal tissues. However, RT efficacy can be attenuated by factors like salient hypoxia found in solid tumors. [12][13][14][15] Moreover, some cancer subtypes and cancer stem cells exhibit high resistance to X-ray radiation. [16] Consequently, the development of radiosensitizers that can sensitize hypoxic or radio-resistant tumors to X-ray radiation [17][18][19][20] has become an area of intense research.The emerging radiosensitizers can be classified into three groups: gasotransmitters (e.g., O 2 , NO, H 2 S, etc.), [21][22][23][24][25] anticancer drugs (e.g., paclitaxel (PTX), docetaxel (Dtxl), topotecan (TPT), etc.), [26][27][28] and high-Z elements (e.g., Au, Ba, Bi, Pt, W, etc.). [29][30][31][32][33][34][35] The gasotransmitters can mimic the radiosensitizing effect of oxygen and downregulate hypoxia-inducible factor-1 alpha (HIF-1α) expression, [23] while anticancer drugs can induce cancer cells to enter the G2/M phase which is the most radiation-sensitive cell-cycle phase. [36] High-Z elements are known for scattering one X-ray beam into several beams to concentrate more radiation on tumors for aggravated radiation damage. [37,38] This radiation dose-amplification effect is based on the Compton scattering mechanism. [39] All of these radiosensitizers are usually loaded or engineered into nanocarriers for tumor-specific delivery or by passive tumor accumulation via the enhanced permeability and retention (EPR) effect. [40] Heretofore, a great number of nanomaterials have been synthesized to pave the way for high-performance radiosensitization for RT enhancement. [41][42][43][44] Despite the appreciable progress achieved in X-ray radiation sensitization/enhancement, RT as a monotherapy generally fails to eliminate the whole tumor as cancer cells can undergo DNA-repair and regrowth. [45,46] As such, current research is gradually shifting from RT monotherapy to X-rayexcited multimodal therapy. This means that two or more therapeutic modalities are simultaneously activated by X-ray to yield synchronous/synergistic anticancer effects. [47][48][49] For example, it has been shown that high-energy X-ray irradiation can triggerThe advancements in nanotechnology have created multifunctional nanomaterials aimed at enhancing diagnostic accuracy and treatment efficacy for cancer. However, the ability to target deep-seated tumors remains one of the most critical challenges for certain nanomedicine applications. To this end, X-ray-excited theranostic techniques provide a means of overcoming the limits of light penetration and tissue attenuation. Herein, a comprehe...

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Section: Introductionmentioning

confidence: 99%

Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics

et al. 2019

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“…High-Z metal-based nanoparticles possess high X-ray photon capture cross-sections and are capable of increasing the production of secondary and Auger electrons, which in turn increases the generated reactive oxygen species (ROS) and enhances radiotherapy. 8,9 In addition to gold nanoparticles, which are the first and most studied nanoparticles and the enhancement effects of which have been demonstrated both in vitro and in vivo, [10][11][12] gadolinium-based nanoparticles (GdNPs) have also attracted substantial attention because of their high relaxation time and high atomic number (Z=64). [13][14][15][16] Ultra-small gadolinium oxide nanocrystals (GONs) are attractive GdNPs that possess a high density of Gd per contrastagent unit (200-400 atoms per particle).…”

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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“…Heavy metal‐based nanoparticles have higher X‐ray absorption coefficients, and even low doses can achieve significant radiosensitization when deposited into tumors. [ 70 ]…”

Section: Radiotherapy and Its Immunomodulatory Effectmentioning

confidence: 99%

Recent Progress of Potentiating Immune Checkpoint Blockade with External Stimuli—an Industry Perspective

Saklatvala

Mittal

et al. 2020

Advanced Science

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The past decade has seen the materialization of immune checkpoint blockade as an emerging approach to cancer treatment. However, the overall response and patient survival are still modest. Various efforts to study the “cancer immunogram” have highlighted complex biology that necessitates a multipronged approach. This includes increasing the antigenicity of the tumor, strengthening the immune infiltration in the tumor microenvironment, removing the immunosuppressive mechanisms, and reducing immune cell exhaustion. The coordination of these approaches, as well as the ability to enhance them through delivery, is evaluated. Due to their success in multiple preclinical models, external‐stimuli‐responsive nanoparticles have received tremendous attention. Several studies report success in distantly located tumor regression, metastases, and reoccurrence in preclinical mouse models. However, clinical translation in this space remains low. Herein, the recent advancement in external‐stimuli‐responsive nanoconstruct‐synergized immune checkpoint blockade is summarized, offering an industry perspective on the limitations of current academic innovations and discussing challenges in translation from a technical, manufacturing, and regulatory perspective. These limitations and challenges will need to be addressed to establish external‐stimuli‐based therapeutic strategies for patients.

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

Cited by 257 publications

References 295 publications

Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics

Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics

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

Recent Progress of Potentiating Immune Checkpoint Blockade with External Stimuli—an Industry Perspective

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