Localized nuclear reaction breaks boron drug capsules loaded with immune adjuvants for cancer immunotherapy

Shi, Yaxin; Guo, Zhifang; Fu, Qiang; Shen, Xinyuan; Zhang, Zhongming; Sun, Wenjun; Wang, Jinqiang; Sun, Junliang; Zhang, Zizhu; Liu, Tong; Gu, Zhen; Liu, Zhibo

doi:10.1038/s41467-023-37253-x

Cited by 22 publications

(31 citation statements)

References 41 publications

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“…The RBE of BNCT based on nanoboron agents could be used to calculate the absorbed dose accurately, thereby reducing the damage wrought to healthy tissues. The impact of reducing boron efflux is far greater than anticipated previously and provides opportunities for selecting many more boron-containing agents. ,, Herein, the use of nanoparticles to “fix” boron has demonstrated the adaptability of nanotechnology for BNCT and clinical drug research. In the future, the kinetics of boron in cells will become important, which means that 20 ppm may no longer be a necessary condition to restrict the development of boron-containing agents.…”

Section: Resultsmentioning

confidence: 99%

Boron-Containing MOF Nanoparticles with Stable Metabolism in U87-MG Cells Combining Microdosimetry To Evaluate Relative Biological Effectiveness of Boron Neutron Capture Therapy

Wang,

Lei,

Zhang

et al. 2024

ACS Appl. Mater. Interfaces

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Accurate prediction of the relative biological effectiveness (RBE) of boron neutron capture therapy (BNCT) is challenging. The therapy is different from other radiotherapy; the dynamic distribution of boron-containing compounds in tumor cells affects the therapeutic outcome considerably and hampers accurate measurement of the neutron-absorbed dose. Herein, we used boron-containing metal−organic framework nanoparticles (BMOFs) with high boron content to target U87-MG cells and maintain the concentration of the 10 B isotope in cells. The content of boron in the cells could maintain 90% (60 ppm) within 20 min compared with that at the beginning; therefore, the accurate RBE of BNCT can be acquired. The effects of BNCT upon cells after neutron irradiation were observed, and the neutron-absorbed dose was obtained by Monte Carlo simulations. The RBE of BMOFs was 6.78, which was 4.1-fold higher than that of a small-molecule boron-containing agent (boric acid). The energy spectrum of various particles was analyzed by Monte Carlo simulations, and the RBE was verified theoretically. Our results suggested that the use of nanoparticle-based boron carriers in BNCT may have many advantages and that maintaining a stable boron distribution within cells may significantly improve the efficiency of BNCT.

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Section: Resultsmentioning

confidence: 99%

Boron-Containing MOF Nanoparticles with Stable Metabolism in U87-MG Cells Combining Microdosimetry To Evaluate Relative Biological Effectiveness of Boron Neutron Capture Therapy

Wang,

Lei,

Zhang

et al. 2024

ACS Appl. Mater. Interfaces

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“…As poly(ethylene glycol) (PEG) is widely used to enhance the biodistribution of nanomedicines, we PEGylated ZnPc (ZnPc@PEG) and ZnPc-PI (ZnPc-PI@PEG) with 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[amino(polyethylene glycol)-2000] for biodistribution analysis . ZnPc@PEG was cleared as rapidly as ZnPc in the bloodstream (Figure S32), likely due to its poor stability under physiological conditions (Figure S36).…”

Section: Resultsmentioning

confidence: 99%

Nanoscale Covalent Organic Framework with Staggered Stacking of Phthalocyanines for Mitochondria-Targeted Photodynamic Therapy

Liu,

Kang,

Fan

et al. 2023

J. Am. Chem. Soc.

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Phthalocyanine photosensitizers (PSs) have shown promise in fluorescence imaging and photodynamic therapy (PDT) of malignant tumors, but their practical application is limited by the aggregation-induced quenching (AIQ) and inherent photobleaching of PSs. Herein, we report the synthesis of a twodimensional nanoscale covalent organic framework (nCOF) with staggered (AB) stacking of zinc-phthalocyanines (ZnPc), ZnPc-PI, for fluorescence imaging and mitochondria-targeted PDT. ZnPc-PI isolates and confines ZnPc PSs in the rigid nCOF to reduce AIQ, improve photostability, enhance cellular uptake, and increase the level of reactive oxygen species (ROS) generation via mitochondrial targeting. ZnPc-PI shows efficient tumor accumulation, which allowed precise tumor imaging and nanoparticle tracking. With high cellular uptake and tumor accumulation, intrinsic mitochondrial targeting, and enhanced ROS generation, ZnPc-PI exhibits potent PDT efficacy with >95% tumor growth inhibition on two murine colon cancer models without causing side effects.

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“…While scientists have discovered that the combination of BNCT and immunotherapy can enhance in vitro effects, their efficacy has often been limited. In 2023, Liu's group 116 designed a neutron-activated boron capsule B-COF (Figure 14), which synergistically combines BNCT with a controlled released immune adjuvant, triggering an effective antitumor immune response. Neutron irradiation has been found to induce defects in the frameworks of the boron capsule, accelerating drug release.…”

Section: Combination With Immunotherapymentioning

confidence: 99%

Section: Synergistic Effect Of Bnct With Other Therapeuticsmentioning

confidence: 99%

The Dawn of a New Era: Tumor-Targeting Boron Agents for Neutron Capture Therapy

Luo,

Huang,

Chu

et al. 2023

Mol. Pharmaceutics

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Cancer is widely recognized as one of the most devastating diseases, necessitating the development of intelligent diagnostic techniques, targeted treatments, and early prognosis evaluation to ensure effective and personalized therapy. Conventional treatments, unfortunately, suffer from limitations and an increased risk of severe complications. In light of these challenges, boron neutron capture therapy (BNCT) has emerged as a promising approach for cancer treatment with unprecedented precision to selectively eliminate tumor cells. The distinctive and promising characteristics of BNCT hold the potential to revolutionize the field of oncology. However, the clinical application and advancement of BNCT technology face significant hindrance due to the inherent flaws and limited availability of current clinical drugs, which pose substantial obstacles to the practical implementation and continued progress of BNCT. Consequently, there is an urgent need to develop efficient boron agents with higher boron content and specific tumor-targeting properties. Researchers aim to address this need by integrating tumor-targeting strategies with BNCT, with the ultimate goal of establishing BNCT as an effective, readily available, and cutting-edge treatment modality for cancer. This review delves into the recent advancements in integrating tumor-targeting strategies with BNCT, focusing on the progress made in developing boron agents specifically designed for BNCT. By exploring the current state of BNCT and emphasizing the prospects of tumor-targeting boron agents, this review provides a comprehensive overview of the advancements in BNCT and highlights its potential as a transformative treatment option for cancer.

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Localized nuclear reaction breaks boron drug capsules loaded with immune adjuvants for cancer immunotherapy

Cited by 22 publications

References 41 publications

Boron-Containing MOF Nanoparticles with Stable Metabolism in U87-MG Cells Combining Microdosimetry To Evaluate Relative Biological Effectiveness of Boron Neutron Capture Therapy

Boron-Containing MOF Nanoparticles with Stable Metabolism in U87-MG Cells Combining Microdosimetry To Evaluate Relative Biological Effectiveness of Boron Neutron Capture Therapy

Nanoscale Covalent Organic Framework with Staggered Stacking of Phthalocyanines for Mitochondria-Targeted Photodynamic Therapy

The Dawn of a New Era: Tumor-Targeting Boron Agents for Neutron Capture Therapy

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