image: Fig 1
Credit: OEA
A new publication from Opto-Electronic Advances; DOI 10.29026/oea.2024.240013, discusses a NIR-triggered on-site NO/ROS/RNS nanoreactor.
Phototherapy is a safe and effective method for tumor treatment, including photothermal therapy (PTT) and photodynamic therapy (PDT). PTT refers to the use of laser to activate photothermal conversion agents and use high temperature to kill tumor cells, while PDT stimulate photosensitizer to produce reactive oxygen species (ROS) to kill tumor cells. Studies have shown the combined therapeutic potential of PTT/PDT, but limited by the low oxygen content in tumors, monotherapy is often insufficient to produce efficient and long-term therapeutic effects on tumors. At the same time, the ability of phototherapy to trigger the immune response against cancer is limited, and local immune stimulation is difficult to activate the systemic anti-tumor immune response. How to improve the ability of phototherapy to stimulate the systemic immune response needs further research.
Nitric oxide (NO) has multiple functions in the physiological and pathological processes of the human body, and a critical interaction occurs between it and reactive oxygen species (ROS) produced by PDT to form reactive nitrogen species (RNS). These RNS could enhance the efficacy of PDT under hypoxic conditions by killing tumor cells, while also significantly affecting the immune response. The current study demonstrates that RNS can suppress immunosuppressive cells and polarize tumor-associated macrophages into M1-like phenotypes. Thus, the strategy of NO/ROS/RNS cascade generation has great potential in activating systemic, long-term anti-tumor immune responses.
However, the generation of RNS is hampered by the difficulty in precisely controlling the location and timing of NO release, as well as the short lifetime (usually 3-6 ms) and limited diffusion range (~ 20 nm) of singlet oxygen. Using nanoparticles to deliver NO donor and photosensitizer at the same time, and applying laser irradiation to the tumor site to initiate PTT/PDT at the same time, we can achieve an on-site cascade of NO/ROS/RNS release, which can significantly improve the production of RNS and anti-tumor efficacy.
The authors of this article propose a NIR trigger-activated reactive nitrogen nanoreactor (PBNO-Ce6), which can simultaneously produce nitric oxide (NO), reactive oxygen species (ROS) and reactive nitrogen species (RNS) on-site to kill tumor cells in vivo, enhance local and systemic long-term anti-tumor immune response, and protect the tissue from the re-attack of tumors.
This nanoreactor is based on Prussian blue nanoparticles (PB). PBNO nanoparticles, which can release NO after laser stimulation, were first synthesized by doping sodium nitroprusside (SNP) in the crystal structure of PB as NO donor, and then the photosensitizer Ce6 was loaded on the surface mesopore of the nanoparticles to achieve PTT/PDT combination therapy. The released NO combines with ROS produced by photosensitizers to RNS, which greatly improves the photodynamic/photothermal therapeutic effect on tumors and activates the anti-tumor immune response, as shown in Figure 1.
It was confirmed that PBNO-Ce6 was warmed up by laser irradiation, and the tumor killing ability of NO combined with ROS was significantly increased in vitro and in vivo compared to monotherapy. As shown in the live-dead cell staining and flow cytometry results in Figure 2, PBNO-Ce6 induced more apoptosis in tumor cells. Of greater interest was its ability to modulate the activation of the immune response, with PBNO-Ce6 treatment leading to a significant 2.7-fold increase in cytotoxic T lymphocytes and a 62% reduction in regulatory T cells compared to control PB-Ce6 (Prussian blue nanoparticles loaded with Ce6), signaling a significant improvement over conventional PTT/PDT, as shown in Figure 3.
PBNO-Ce6 acts as an unprecedented NIR-triggered RNS nanoreactor with synergistic photodynamic/photothermal effects and potent immunostimulatory activity. This design strategy can be used as a versatile platform in combination with immune checkpoint inhibitors or chemotherapy to further improve the prognosis of malignancies.
Keywords: photothermal therapy / photodynamic therapy / nitric oxide / reactive nitrogen species / triple-negative breast cancer / immune response / nanoreactor
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The Molecular Imaging Laboratory of Nanjing Medical University is based on the School of Medical Imaging of Nanjing Medical University. Professor Shouju Wang, the director of the laboratory, is a recipient of the National Natural Science Foundation of China's Excellent Youth Programme and an Outstanding Young Radiologist of Jiangsu Province. Professor Wang studied at Nanjing University and was awarded the first Zhong Nanshan Youth Science and Technology Innovation Award in 2021. Main research interests include tumor photodiagnosis and phototherapeutic technology, integrated nanoprobes for tumor diagnosis and treatment, and AI-assisted nanomedicine design. He has published more than 40 papers in Adv Mater, ACS Nano, Nano Lett and so on. As a member of Molecular Imaging Committee of Chinese Radiological Society, he is also the first young editorial board member of Fundamental Research, an official journal of Natural Science Foundation of China.
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Opto-Electronic Advances (OEA) is a rapidly growing high-impact, open access, peer reviewed monthly SCI journal with an impact factor of 14.1 (Journal Citation Reports for IF2022). Since its launch in March 2018, OEA has been indexed in SCI, EI, DOAJ, Scopus, CA and ICI databases over the time, and expanded its Editorial Board to 30 members from 17 countries.
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Xu ZQ, Kang YK, Zhang J et al. NIR-triggered on-site NO/ROS/RNS nanoreactor: Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation. Opto-Electron Adv 7, 240013 (2024). doi: 10.29026/oea.2024.240013
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Opto-Electronic Advances