实用医学杂志 ›› 2022, Vol. 38 ›› Issue (16): 2024-2030.doi: 10.3969/j.issn.1006⁃5725.2022.16.008

• 基础研究 • 上一篇    下一篇

碳酸钙纳米粒子用于靶向光动力治疗胰腺癌的实验研究

郭坤雄 王志华 郭婵娟 范应方    

  1. 南方医科大学珠江医院肝胆一科(广州510280)

  • 出版日期:2022-08-25 发布日期:2022-08-25
  • 通讯作者: 范应方 E⁃mail:fanxifan@smu.edu.cn
  • 基金资助:
    广州市科技计划资助项目(编号:202206010093);广东省重点领域研发计划资助项目(编号:2020B010165004)

Targeting photodynamic therapy using calcium carbonate nanoparticles against pancreatic cancer

GUO Kunxiong,WANG Zhihua,GUO Chanjuan,FAN Yingfang.   

  1. Department of Hepatobiliary SurgeryZhujiang Hospi⁃ talSouthern Medical UniversityGuangzhou 510280China
  • Online:2022-08-25 Published:2022-08-25
  • Contact: FAN Yingfang E⁃mail:fanxifan@smu.edu.cn

摘要:

目的 观察碳酸钙纳米粒子靶向光动力治疗胰腺癌的疗效,并对其作用机制进行探索。 方法 采用气体扩散法制备装载光敏剂二氢卟吩 e6(chlorine e6,Ce6)纳米粒子 Ce6@CaCO3,聚乙二醇修 饰后,物理吸附胰岛素样生长因子 1 受体(insulin⁃like growth factor 1 receptor,IGF⁃1R)的配体 Linsitinib,最 终合成酸响应的主动靶向型纳米粒子 Ce6/Lins@CaCO3⁃PEG(CLCP),并进行理化性质表征。通过细胞和动 物实验,观察 CLCP 主动靶向性及光动力治疗胰腺癌的效果。结果 CLCP 水合粒径为(121.5 ± 5.2)nm,电 镜下呈均匀分散的球形;CLCP Ce6 的包封率为 63.2%、包载率为 16.37%;CLCP 在酸性(pH=6.5)环境下 可迅速降解。细胞摄取实验表明胰腺癌细胞对 CLCP 摄取较非靶向组明显增多(P < 0.001);活/死细胞染 色及 CCK⁃8 实验表明,与非靶向组比较,CLCP 光动力治疗后胰腺癌细胞活力明显下降(P < 0.01)、死亡增 多(P < 0.001)。CLCP 光动力治疗组小鼠生存期明显延长,病理提示肿瘤组织细胞凋亡增多,且流式细胞 术表明肿瘤组织中 CD8+ T 细胞比例增大。结论 成功构建了基于 IGF⁃1R 的碳酸钙纳米粒子 CLCP,靶向 递送光敏剂Ce6并介导光动力治疗直接杀伤肿瘤细胞和激活抗肿瘤免疫,有效抑制了胰腺癌的生长,为胰 腺癌的治疗提供了新思路。 

关键词: 胰腺癌,  , 碳酸钙,  , 纳米粒子,  , 光动力治疗

Abstract:

Objective The aim of this study was to explore the therapeutic effect and potential mechanism of targeting photodynamic therapy using calcium carbonate nanoparticles in pancreatic cancer. Methods Ce6@Ca⁃ CO3 were prepared by gas diffusion method to load Ce6,and then modified with polyethylene glycol. Linsitinib was used to target insulin⁃like growth factor 1 receptor(IGF⁃1R)to prepare CLCP nanoparticles with acid⁃responsive and active targeting abilities. The characterization of CLCP was investigated. The active targeting ability and the therapeutic effect of CLCP were evaluated in vitro and in vivo. Results The average hydrated size of CLCP was (121.5 ± 5.2)nm with spherical shape under the electron microscope. The loading efficiency of Ce6 was 63.2% and the loading content was 16.37%. CLCP degraded rapidly in a weak acidic(pH = 6.5)environment. Pancreatic cancer cells have increased uptake of CLCP(P < 0.001). CLCP⁃mediated photodynamic therapy decreased cell viability(P < 0.01)by inducing wider cells death compared with untargeted group(P < 0.001). CLCP⁃mediated photodynamic therapy effectively prolonged the survival period of mice and pathologically caused cancer cells apoptosis increased. Besides,CLCP ⁃mediated photodynamic therapy enhanced the recruitment of CD8 + T cells in tumors. Conclusion We successfully synthesized the targeting CLCP based on IGF⁃1R to efficiently deliver Ce6 and CLCP⁃mediated photodynamic therapy has satisfactory therapeutic effect due to the direct killing of cancer cells and the activation of anti⁃tumor immune,which provides a novel strategy for pancreatic cancer treatment. 

Key words:

pancreatic cancer, calcium carbonate, nanoparticles, photodynamic therapy

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