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Antioxidant-photosensitizer dual-loaded polymeric micelles with controllable production of reactive oxygen species

机译:可控制生产活性氧的抗氧化剂-光敏剂双负载聚合物胶束

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Poly(ethylene glycol)-b-poly(caprolactone) (PEG-b-PCL) micelles dually loaded with both pheophorbide a (PhA) as a photosensitizer and beta-carotene (CAR) as a singlet oxygen (O-1(2)) scavenger were designed to control photodynamic therapy (PDT) activity in cancer treatment. The CAR in the PhA/CAR micelles significantly diminished PhA-generated O-1(2) through direct O-1(2) scavenging, whereas the CAR molecules lost their O-1(2) scavenging activity when the PhA and CAR were spatially isolated by the disintegration of the PEG-b-PCL micelles. In cell-culture systems, light irradiation at a post-treatment time that corresponded to the presence of the micelles in the blood environment induced negligible phototoxicity, whereas light irradiation at a post-treatment time that corresponded to the presence of the micelles in the intracellular environment induced remarkable phototoxicity. In addition, a longer post-treatment time induced greater internalization of PhA/CAR micelles, which resulted in higher phototoxicity, suggesting an increase in photo killing activity against the tumor cells of interest. Thus, the co-loading of a O-1(2) generator and a O-1(2) scavenger into a single micelle is a potential strategy that may be useful in facilitating more accurate and reliable PDT with site-specific controllable production of singlet oxygen species for cancer treatment. (C) 2014 Elsevier B.V. All rights reserved.
机译:聚(乙二醇)-b-聚己内酯(PEG-b-PCL)胶束双重负载脱镁叶绿酸a(PhA)作为光敏剂和β-胡萝卜素(CAR)作为单线态氧(O-1(2)清除剂旨在控制癌症治疗中的光动力疗法(PDT)活性。 PhA / CAR胶束中的CAR通过直接清除O-1(2)大大减少了PhA生成的O-1(2),而当PhA和CAR在空间上时,CAR分子失去了其O-1(2)清除活性。通过PEG-b-PCL胶束的分解分离。在细胞培养系统中,对应于血液环境中胶束存在的后处理时间的光照射可忽略不计的光毒性,而对应于细胞内胶束存在的后处理时间的光照射可忽略不计。环境引起显着的光毒性。另外,更长的后处理时间诱导了PhA / CAR胶束的更大内在化,这导致了更高的光毒性,这表明针对目标肿瘤细胞的光杀伤活性增加。因此,将O-1(2)生成器和O-1(2)清除剂共同装载到单个胶束中是一种潜在的策略,可能有助于促进更精确,更可靠的PDT的生产,且该方法在特定地点可控生产单线态氧用于癌症治疗。 (C)2014 Elsevier B.V.保留所有权利。

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