海藻酸钠前药纳米粒在肿瘤光动力治疗中的应用研究

秦怡博; 杨鹏翔; 时圣彬; 孙洪范; 张闯年; 孔德领

doi:10.11777/j.issn1000-3304.2018.18039

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海藻酸钠前药纳米粒在肿瘤光动力治疗中的应用研究

研究论文 | 更新时间：2021-01-26

- 海藻酸钠前药纳米粒在肿瘤光动力治疗中的应用研究
- Redox-sensitive Alginate Prodrug Nanoparticles for Tumor Photodynamic Therapy
- 高分子学报 2018年0卷第7期页码：909-916
- 作者机构：
  
  1.生物医学工程研究所天津市生物医用材料重点实验室中国医学科学院北京协和医学院　天津 300192
  2.生物活性材料教育部重点实验室药物化学生物学国家重点实验室南开大学生命科学学院　天津 300071
- 作者简介：
  
  E-mail: cnzhang@mail.nankai.edu.cn Chuang-nian Zhang, E-mail: cnzhang@mail.nankai.edu.cn
  E-mail: kongdeling@nankai.edu.cn De-ling Kong, E-mail: kongdeling@nankai.edu.cn
- 基金信息：
  
  国家自然科学基金(基金号 21604095)和中国医学科学院医学与健康科技创新工程项目(项目号 2017-I2M-3-022)资助()
- DOI：10.11777/j.issn1000-3304.2018.18039
  中图分类号：
- 纸质出版日期：2018-7，
  
  收稿日期：2018-2-2，
  
  修回日期：2018-3-3，
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秦怡博, 杨鹏翔, 时圣彬, 孙洪范, 张闯年, 孔德领. 海藻酸钠前药纳米粒在肿瘤光动力治疗中的应用研究[J]. 高分子学报, 2018,0(7):909-916.

Yi-bo Qin, Peng-xiang Yang, Sheng-bin Shi, Hong-fan Sun, Chuang-nian Zhang, De-ling Kong. Redox-sensitive Alginate Prodrug Nanoparticles for Tumor Photodynamic Therapy[J]. Acta Polymerica Sinica, 2018,0(7):909-916.
秦怡博, 杨鹏翔, 时圣彬, 孙洪范, 张闯年, 孔德领. 海藻酸钠前药纳米粒在肿瘤光动力治疗中的应用研究[J]. 高分子学报, 2018,0(7):909-916. DOI： 10.11777/j.issn1000-3304.2018.18039.

Yi-bo Qin, Peng-xiang Yang, Sheng-bin Shi, Hong-fan Sun, Chuang-nian Zhang, De-ling Kong. Redox-sensitive Alginate Prodrug Nanoparticles for Tumor Photodynamic Therapy[J]. Acta Polymerica Sinica, 2018,0(7):909-916. DOI： 10.11777/j.issn1000-3304.2018.18039.

摘要

利用具有还原敏感性的胱胺将疏水性光敏剂脱镁叶绿酸盐A (PheoA)偶联到天然多糖海藻酸钠(ALG)上，得到同时具有光敏性和还原敏感性的两亲性多糖前药(PheoA-ALG)，再通过疏水相互作用自组装形成前药纳米粒(PheoA-ALG NPs)，应用于肿瘤光动力治疗. 对PheoA-ALG NPs的理化性质进行了评价，体外考察PheoA-ALG NPs的释药行为、细胞胞吞及胞内ROS，并重点研究了PheoA-ALG NPs的体外细胞毒性以及体内抑瘤活性.

Abstract

Nanoparticles have been extensively explored as an effective means to deliver photosensitizers for photodynamic therapy (PDT) against cancer. In this work

Pheophorbide A (PheoA)

a hydrophobic photosensitizer

was conjugated to natural polysaccharide alginate (PheoA-ALG)

via

a redox-sensitive disulfide linkage. The critical aggregation concentration (CAC) of PheoA-ALG in aqueous solution was 73.51 μg/mL

detected by pyrene monomer fluorescence probe technology. The resulting amphiphilic PheoA-ALG could form self-assembled nanoparticles (PheoA-ALG NPs) in an aqueous medium as prodrug nanoparticles for tumor photodynamic therapy. The physical and chemical properties of PheoA-ALG NPs were studied. TEM and DLS revealed that PheoA-ALG NPs were monodisperse spherical structures with a hydrodynamic diameter about 198 nm. PheoA release profiles

in vitro

indicated that PheoA release from PheoA-ALG NPs was redox-sensitive. Whereafter

the cellular uptake and cytotoxicity of PheoA-ALG NPs were investigated

in vitro

. Cellular uptake results showed that PheoA-ALG NPs were readily taken up by B16 tumor cells and enhanced PheoA uptake was detectable in PheoA-ALG NPs-treated B16 cells in comparison to carrier free drugs. Under light irradiation

PheoA-ALG NPs also elicited intracellular ROS generation

which led to an enhanced toxicity in B16 cells both

in vitro

and

in vivo

. The CCK-8 assay showed that PheoA-ALG NPs had good cellular compatibility without cytotoxic

in vitro

without light irradiation

and PheoA-ALG NPs exhibited light dependent cytotoxic response to B16 cells. After light irradiation

IC50 of PheoA-ALG NPs decreased to 0.16 μg mL

−1

which was about 0.67-fold lower than those of the free PheoA groups with light irradiation.

In vivo

anti-tumor efficacy of PheoA-ALG NPs was assessed using B16 tumor-bearing mice. Notably

mice treated with PheoA-ALG NPs under light irradiation displayed the highest inhibition ratio of 72.8%

among those treated with free PheoA (45.8%). These results suggest that PheoA-ALG NPs have good potential for tumor photodynamic therapy.

关键词

海藻酸钠还原敏感性前药纳米粒光动力治疗

Keywords

AlginateRedox-sensitiveProdrug nanoparticlePhotodynamic therapy

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