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- 저자 : Terman, Mohammad Sadegh (검색결과 2 건)
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Choe, S.w.,Terman, D.S.,Rivers, A.E.,Rivera, J.,Lottenberg, R.,Sorg, B.S. Elsevier Science Publishers 2013 Journal of controlled release Vol.171 No.2
Selective drug delivery to hypoxic tumor niches remains a significant therapeutic challenge that calls for new conceptual approaches. Sickle red blood cells (SSRBCs) have shown an ability to target such hypoxic niches and induce tumoricidal effects when used together with exogenous pro-oxidants. Here we determine whether the delivery of a model therapeutic encapsulated in murine SSRBCs can be enhanced by ex vivo photosensitization under conditions that delay autohemolysis to a time that coincides with maximal localization of SSRBCs in a hypoxic tumor. Hyperspectral imaging of 4T1 carcinomas shows oxygen saturation levels <10% in a large fraction (commonly 50% or more) of the tumor. Using video microscopy of dorsal skin window chambers implanted with 4T1 tumors, we demonstrate that allogeneic SSRBCs, but not normal RBCs (nRBCs), selectively accumulate in hypoxic 4T1 tumors between 12 and 24h after systemic administration. We further show that ex vivo photo-oxidation can program SSRBCs to postpone hemolysis/release of a model therapeutic to a point that coincides with their maximum sequestration in hypoxic tumor microvessels. Under these conditions, drug-loaded photosensitized SSRBCs show a 3-4 fold greater drug delivery to tumors compared to non-photosensitized SSRBCs, drug-loaded photosensitized nRBCs, and free drug. These results demonstrate that photo-oxidized SSRBCs, but not photo-oxidized nRBCs, sequester and hemolyze in hypoxic tumors and release substantially more drug than photo-oxidized nRBCs and non-photo-oxidized SSRBCs. Photo-oxidation of drug-loaded SSRBCs thus appears to exploit the unique tumor targeting and carrier properties of SSRBCs to optimize drug delivery to hypoxic tumors. Such programmed and drug-loaded SSRBCs therefore represent a novel and useful tool for augmenting drug delivery to hypoxic solid tumors.
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Saghafi, Mahdi,Ayyoubzadeh, Seyed Mohsen,Terman, Mohammad Sadegh Korean Nuclear Society 2020 Nuclear Engineering and Technology Vol.52 No.12
This paper deals with the simulation-based design optimization and experimental validation of the characteristics of an in-core silver Self-Powered Neutron Detector (SPND). Optimized dimensions of the SPND are determined by combining Monte Carlo simulations and analytical methods. As a first step, the Monte Carlo transport code MCNPX is used to follow the trajectory and fate of the neutrons emitted from an external source. This simulation is able to seamlessly integrate various phenomena, including neutron slowing-down and shielding effects. Then, the expected number of beta particles and their energy spectrum following a neutron capture reaction in the silver emitter are fetched from the TENDEL database using the JANIS software interface and integrated with the data from the first step to yield the origin and spectrum of the source electrons. Eventually, the MCNPX transport code is used for the Monte Carlo calculation of the ballistic current of beta particles in the various regions of the SPND. Then, the output current and the maximum insulator thickness to avoid breakdown are determined. The optimum design of the SPND is then manufactured and experimental tests are conducted. The calculated design parameters of this detector have been found in good agreement with the obtained experimental results.
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