Molecular Imaging Investigations of Polymer-Coated Cerium Oxide Nanoparticles as a Radioprotective Therapeutic Candidate.
Molecular Imaging Investigations of Polymer-Coated Cerium Oxide Nanoparticles as a Radioprotective Therapeutic Candidate.
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DOI：
10.3390/pharmaceutics15082144
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发表时间：
2023-08-15
期刊：
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
--
作者：
氧化铈纳米颗粒 (CONP) 具有独特的表面氧化还原化学性质，似乎可以选择性地保护正常组织免受辐射引起的损伤。我们之前探索聚合物涂层 CONP 生物相容性的研究发现，由于改善了全身生物分布和快速肾脏清除，因此有必要对聚丙烯酸 (PAA) 涂层 CONP 进行进一步研究。本工作进一步探讨了 PAA-CONPs 的放射防护功效以及与肿瘤微环境 pH 相关的作用机制。使用离体 TUNEL 测定来测量 PAA-CONP 对受辐射小鼠结肠的保护作用，并与已建立的放射防护剂氨磷汀进行比较。利用自发性结肠肿瘤的[18F]FDG PET成像来确定PAA-CONP对肿瘤放射反应的影响。使用体内 MRI 和离体克隆形成测定来确定 pH 对 PAA-CONP 在受辐射的荷瘤小鼠中的辐射防护作用的影响。 PAA-CONPs 在正常结肠中表现出优异的放射防护功效，相当于未包被的 CONPs 和氨磷汀。 [18F]FDG PET 成像显示 PAA-CONP 不影响肿瘤对放射的反应。肿瘤 pH 值正常化使得 PAA-CONP 对肿瘤具有一定的放射防护作用，这可能解释了它们在酸性肿瘤微环境中缺乏肿瘤放射防护作用。总体而言，PAA-CONP 符合作为放射防护治疗剂的临床应用标准，并且是进一步研究的优秀候选者。
Cerium oxide nanoparticles (CONPs) have a unique surface redox chemistry that appears to selectively protect normal tissues from radiation induced damage. Our prior research exploring the biocompatibility of polymer-coated CONPs found further study of poly-acrylic acid (PAA)-coated CONPs was warranted due to improved systemic biodistribution and rapid renal clearance. This work further explores PAA-CONPs’ radioprotective efficacy and mechanism of action related to tumor microenvironment pH. An ex vivo TUNEL assay was used to measure PAA-CONPs’ protection of the irradiated mouse colon in comparison to the established radioprotector amifostine. [18F]FDG PET imaging of spontaneous colon tumors was utilized to determine the effects of PAA-CONPs on tumor radiation response. In vivo MRI and an ex vivo clonogenic assay were used to determine pH effects on PAA-CONPs’ radioprotection in irradiated tumor-bearing mice. PAA-CONPs showed excellent radioprotective efficacy in the normal colon that was equivalent to uncoated CONPs and amifostine. [18F]FDG PET imaging showed PAA-CONPs do not affect tumor response to radiation. Normalization of tumor pH allowed some radioprotection of tumors by PAA-CONPs, which may explain their lack of tumor radioprotection in the acidic tumor microenvironment. Overall, PAA-CONPs meet the criteria for clinical application as a radioprotective therapeutic agent and are an excellent candidate for further study.
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影响因子：
45.3
作者：
Brizel, DM;Wasserman, TH;Sauer, R
通讯作者：
Sauer, R
影响因子：
5.4
作者：
Emam MH;Elezaby RS;Swidan SA;Loutfy SA;Hathout RM
通讯作者：
Hathout RM
影响因子：
4.1
作者：
Datta, Aparna;Mishra, Snehasis;Roy, Somenath
通讯作者：
Roy, Somenath
DOI：
10.1590/s0100-879x2000000700009
发表时间：
2000-07-01
影响因子：
2.3
作者：
De Souza, CA;Santini, G;Damasio, E
通讯作者：
Damasio, E
影响因子：
9.5
作者：
Baldim, Victor;Yadav, Nisha;Berret, Jean-Francois
通讯作者：
Berret, Jean-Francois