Hypoxic Radiosensitizer-Lipid Coated Gold Nanoparticles Enhance the Effects of Radiation Therapy on Tumor Growth

Zhao, Zongren; Xu, Haoyue; Li, Shun; Han, Yuhan; Jia, Jinping; Han, Zhengzhong; Zhang, Deyun; Zhang, Longzhen; Yu, Rutong; Liu, Hongmei

doi:10.1166/jbn.2019.2830

Cited by 7 publications

(5 citation statements)

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“…Hypoxia and acidic pH, common features in the tumor microenvironment (TME), reduce the sensitivity of tumor cells to anticancer drugs and the reactivity to free radicals, causing hurdles in cancer therapy. [142][143][144][145][146] Hence, several features of TME can be used to design active-targeting methods. 143,144,147,148 For example, the acidic pH of TME effectively internalizes pH-sensitive nanocarriers into cancer cells and releases their therapeutic payload.…”

Section: Tumor Microenvironment Targeted Gnpsmentioning

confidence: 99%

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<p>Gold Nanoparticles as Radiosensitizers in Cancer Radiotherapy</p>

Chen

Yang

Shao

et al. 2020

IJN

177

191

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The rapid development of nanotechnology offers a variety of potential therapeutic strategies for cancer treatment. High atomic element nanomaterials are often utilized as radiosensitizers due to their unique photoelectric decay characteristics. Among them, gold nanoparticles (GNPs) are one of the most widely investigated and are considered to be an ideal radiosensitizers for radiotherapy due to their high X-ray absorption and unique physicochemical properties. Over the last few decades, multidisciplinary studies have focused on the design and optimization of GNPs to achieve greater dosing capability and higher therapeutic effects and highlight potential mechanisms for radiosensitization of GNPs. Although the radiosensitizing potential of GNPs has been widely recognized, its clinical translation still faces many challenges. This review analyses the different roles of GNPs as radiosensitizers in cancer radiotherapy and summarizes recent advances. In addition, the underlying mechanisms of GNP radiosensitization, including physical, chemical and biological mechanisms are discussed, which may provide new directions for the optimization and clinical transformation of next-generation GNPs.

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Section: Tumor Microenvironment Targeted Gnpsmentioning

confidence: 99%

“…[142][143][144][145][146] Hence, several features of TME can be used to design active-targeting methods. 143,144,147,148 For example, the acidic pH of TME effectively internalizes pH-sensitive nanocarriers into cancer cells and releases their therapeutic payload. 149,150 Given the acidic pH of TME, Antosh et al 151…”

Section: Tumor Microenvironment Targeted Gnpsmentioning

confidence: 99%

<p>Gold Nanoparticles as Radiosensitizers in Cancer Radiotherapy</p>

Chen

Yang

Shao

et al. 2020

IJN

177

191

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“…However, among other materials, employing GNPs as a radiosensitizing agent has attracted more attention due to their high atomic number ( Z Au = 79), biocompatibility, higher circulation lifetime, and the possibility of tumor targeting (Hainfeld et al 2004 ; Schuemann et al 2016 ). Previous studies have shown radiosensitizing properties of GNPs using keV and clinically relevant MeV energy photons (Chithrani et al 2010 ; Tudda et al 2022 ; Zhao et al 2019 ). This radiosensitization due to GNPs is attributed to increased photoelectric photon absorption, particularly at kilovoltage photon energies, by high-Z materials compared with soft tissue.…”

Section: Introductionmentioning

confidence: 99%

Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics

Jackson,

Hill,

Alhussan

et al. 2023

Cancer Nano

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Background Radiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX. Results The introduction of DTX to GNP-enhanced radiotherapy further increased the radiotherapeutic effects experienced by cancer cells. A 38% increase in DNA double-strand breaks was observed with the combination of GNP/DTX vs GNP alone after a dose of 2 Gy was administered. In vivo results displayed significant reduction in tumor growth over a 30-day observation period with the treatment of GNP/DTX/RT when compared to GNP/RT after a single 5 Gy dose was given to mice. The treatment strategy also resulted in 100% mice survival, which was not observed for other treatment conditions. Conclusions Incorporating DTX to work in unison with GNPs and RT can increase the efficacy of RT treatment. Our study suggests that the treatment strategy could improve tumor control through local dose enhancement. As the concentrations used in this study are clinically feasible, there is potential for this strategy to be translated into clinical settings.

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“…In this way, gold nanospheres [55], nanorods [56], and nanoprisms [57] have been directed to the brain in animal models. For example, Angiopep-2-modified hypoxic lipid radiosensitizer-coated gold NPs were shown to enhance the effects of radiation therapy on brain tumor growth in vivo [58].…”

Section: Angiopep-2-decorated Nanoparticlesmentioning

confidence: 99%

Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review

Habib

Singh

2022

Polymers

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Nanotechnology has opened up a world of possibilities for the treatment of brain disorders. Nanosystems can be designed to encapsulate, carry, and deliver a variety of therapeutic agents, including drugs and nucleic acids. Nanoparticles may also be formulated to contain photosensitizers or, on their own, serve as photothermal conversion agents for phototherapy. Furthermore, nano-delivery agents can enhance the efficacy of contrast agents for improved brain imaging and diagnostics. However, effective nano-delivery to the brain is seriously hampered by the formidable blood–brain barrier (BBB). Advances in understanding natural transport routes across the BBB have led to receptor-mediated transcytosis being exploited as a possible means of nanoparticle uptake. In this regard, the oligopeptide Angiopep-2, which has high BBB transcytosis capacity, has been utilized as a targeting ligand. Various organic and inorganic nanostructures have been functionalized with Angiopep-2 to direct therapeutic and diagnostic agents to the brain. Not only have these shown great promise in the treatment and diagnosis of brain cancer but they have also been investigated for the treatment of brain injury, stroke, epilepsy, Parkinson’s disease, and Alzheimer’s disease. This review focuses on studies conducted from 2010 to 2021 with Angiopep-2-modified nanoparticles aimed at the treatment and diagnosis of brain disorders.

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Hypoxic Radiosensitizer-Lipid Coated Gold Nanoparticles Enhance the Effects of Radiation Therapy on Tumor Growth

Cited by 7 publications

References 0 publications

<p>Gold Nanoparticles as Radiosensitizers in Cancer Radiotherapy</p>

<p>Gold Nanoparticles as Radiosensitizers in Cancer Radiotherapy</p>

Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics

Angiopep-2-Modified Nanoparticles for Brain-Directed Delivery of Therapeutics: A Review

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