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- Duan, Dongban, et al.
(författare)
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Gadolinium Neutron Capture Reaction-Induced Nucleodynamic Therapy Potentiates Antitumor Immunity
- 2023
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Ingår i: CCS Chemistry. - : Chinese Chemical Society. - 2096-5745. ; 5:11, s. 2589-2602
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Tidskriftsartikel (refereegranskat)abstract
- A nuclear reaction-induced dynamic therapy, denoted as nucleodynamic therapy (NDT), has been invented that triggers immunogenic cell death and successfully treats metastatic tumors due to its unexpected abscopal effect. Gadolinium neutron capture therapy (GdNCT) is binary radiotherapy based on a localized nuclear reaction that produces high-energy radiations (e.g., Auger electrons, γ-rays, etc.) in cancer cells when 157Gd is irradiated with thermal neutrons. Yet, its clinical application has been postponed due to the poor ability of Auger electrons and γ-rays to kill cells. Here, we engineered a 157Gd-porphyrin framework that synergizes GdNCT and dynamic therapy to efficiently produce both •OH and immunogenic 1O2 in cancer cells, thereby provoking a strong antitumor immune response. This study unveils the fact and mechanism that NDT heats tumor immunity. Another unexpected finding is that the Auger electron can be the most effective energy-transfer medium for radiation-induced activation of nanomedicines because its nanoscale trajectory perfectly matches the size of nanomaterials. In mouse tumor models, NDT causes nearly complete regression of both primary and distant tumor grafts. Thus, this 157Gd-porphyrin framework radioenhancer endows GdNCT with the exotic function of triggering dynamic therapy; its application may expand in clinics as a new radiotherapy modality that utilizes GdNCT to provoke whole-body antitumor immune response for treating metastases, which are responsible for 90% of all cancer deaths.
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| 2. |
- Tian, Lin, et al.
(författare)
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Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway
- 2016
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Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 60:6, s. 731-747
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Tidskriftsartikel (refereegranskat)abstract
- Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition in olfactory mucosa on particle size implies that the occupation deposition of welding fume manganese can be expected to vary with welding method.
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