无载体水溶性聚卟啉纳米粒用于肿瘤的光动力治疗
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国家自然科学基金项目(面上项目,重点项目,重大项目)


Carrier-free water-soluble polyporphyrin nanoparticles for anti-tumor photodynamic therapy
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The National Natural Science Foundation of China (General Program, Key Program, Major Research Plan)

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    摘要:

    光敏剂是光动力治疗的核心要素,普遍具有大环共轭结构。为了解决大环共轭类光敏剂存在的聚集诱导猝灭(ACQ)效应与强疏水性,本文引入不用长度的醚基柔性链合成了一系列水溶性聚卟啉(P-1O, P-3O, 和P-5O),其中,P-5O具有最优的水溶性、最高的单线态氧产率(单线态氧产率是四羧基苯基卟啉单体的1.95倍);在不借助外源载体的情况下自组装形成粒径在100 nm左右纳米粒,该纳米粒具有良好的pH稳定性、血清稳定性、稀释稳定性、冻干稳定性以及时间稳定性。本文对P-5O纳米粒进行了体外光暗毒性表征,结果表明,P-5O纳米粒在肿瘤细胞(Hep1-6)以及正常细胞(293T)中均具有较低的暗毒性(细胞存活率80%以上),并且在Hep1-6中具有明显的光毒性(细胞存活率低于30%),具有典型的光动力杀伤肿瘤的效果。

    Abstract:

    Photosensitizers played crucial roles in photodynamic therapy (PDT) and most of them owned the macrocyclic and conjugated structures, which would lead to undesired aggregation-induced quenching (ACQ) effect. To solve the ubiquitous ACQ effect and strong hydrophobicity of photosensitizers, in this work, a series of water-soluble polyporphyrins (P-1O, P-3O, and P-5O) were prepared using different flexible chains containing ether groups. Upon screening, P-5O owned best water-solubility, highest singlet oxygen yield (1.95 folds vs porphyrin monomer), and could self-assembled into nanoparticles (NPs) with the particle size of 100 nm in a carrier-free manner. Such NPs had excellent stability upon different pH values, serum, dilution folds, freeze-drying, and incubation time. In vitro photo/dark toxicity results indicated that the NPs had low dark-toxicity in both tumor cells (Hep1-6) and normal cells (293T) (cell viability higher than 80%). The NPs had obvious photo-toxicity in Hep1-6 cells(cell viability fewer than 30%), indicating the typical anti-cancer PDT effect.

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杜梦,徐翔,姜珊,郑楠,刘德华,宋汪泽.无载体水溶性聚卟啉纳米粒用于肿瘤的光动力治疗[J].精细化工,2022,39(3):0

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  • 收稿日期:2021-08-12
  • 最后修改日期:2021-10-26
  • 录用日期:2021-10-27
  • 在线发布日期: 2021-12-06
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