中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (12): 1817-1823.doi: 10.12307/2023.032

• 药物控释材料 drug delivery materials • 上一篇    下一篇

载吲哚菁绿聚乳酸-羟基乙酸共聚物微球的表征及其光热效应

范亚茹1,2,李瑞欣2,李凤集2,罗  睿2,刘  浩2,严颖彬2   

  1. 1天津医科大学口腔临床学院,天津市  300070;2南开大学附属口腔医院,天津市口腔医院,天津市口腔功能重建重点实验室,天津市  300041
  • 收稿日期:2021-12-03 接受日期:2022-01-15 出版日期:2023-04-28 发布日期:2022-07-30
  • 通讯作者: 刘浩,博士,主任医师,南开大学附属口腔医院,天津市口腔医院,天津市口腔功能重建重点实验室,天津市 300041 严颖彬,博士,主任医师,南开大学附属口腔医院,天津市口腔医院,天津市口腔功能重建重点实验室,天津市 300041
  • 作者简介:范亚茹,女,1994年生,山东省菏泽市人,汉族,天津医科大学在读硕士,主要从事口腔颌面部肿瘤的光热治疗研究。
  • 基金资助:
    天津市科技计划项目(19ZXDBSY00070),项目负责人:刘浩;国家自然科学基金(11972198),项目负责人:李瑞欣;天津市临床医学重点学科专项(HWZX001),项目负责人:刘浩

Characterization and photothermal effect of indocyanine green encapsulated poly lactic acid-co-glycolic acid microspheres

Fan Yaru1, 2, Li Ruixin2, Li Fengji2, Luo Rui2, Liu Hao2, Yan Yingbin2   

  1. 1School of Stomatology, Tianjin Medical University, Tianjin 300070, China; 2Affiliated Stomatological Hospital of Nankai University, Tianjin Stomatological Hospital, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin 300041, China
  • Received:2021-12-03 Accepted:2022-01-15 Online:2023-04-28 Published:2022-07-30
  • Contact: Liu Hao, MD, Chief physician, Affiliated Stomatological Hospital of Nankai University, Tianjin Stomatological Hospital, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin 300041, China Yan Yingbin, MD, Chief physician, Affiliated Stomatological Hospital of Nankai University, Tianjin Stomatological Hospital, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin 300041, China
  • About author:Fan Yaru, Master candidate, School of Stomatology, Tianjin Medical University, Tianjin 300070, China; Affiliated Stomatological Hospital of Nankai University, Tianjin Stomatological Hospital, Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin 300041, China
  • Supported by:
    the Tianjin Science and Technology Project, No. 19ZXDBSY00070 (to LH); the National Natural Science Foundation of China, No. 11972198 (to LRX); the Special Project of Tianjin Clinical Medicine Key Discipline, No. HWZX001 (to LH)

摘要:

文题释义:
光热治疗:是治疗肿瘤的一种新兴手段,主要工作原理是通过光热转换剂吸收的近红外光转换为热量,局部升温来消融肿瘤细胞,具有经济可行性、微创性和避免非靶区损伤等明显优势,对人体正常组织产生的不良反应很小,被国际专家学者称为“绿色疗法”。
近红外光:是介于可见光和中红外光之间的电磁波,波长范围为750-2 500 nm,习惯上又将近红外区分为近红外一窗(650-1 000 nm)和近红外二窗(1 000-1 400 nm)2个区域。光热治疗中所采用的激光光源需要对生物组织具有较好的通透性,而第一生物窗口和第二生物窗口激光对组织具有较强的穿透性,尤其是近红外一窗激光研究最为广泛,所以,光热治疗技术中所采用的激光光源一般是808 nm和980 nm等近红外光。

背景:吲哚菁绿作为高效的光热转换剂可用于口腔鳞状细胞癌的光热治疗,但其具有水不稳定和光降解等缺点,利用载体负载吲哚菁绿提高其稳定性,对探索口腔鳞状细胞癌的光热治疗研究具有重要意义。  
目的:制备聚乳酸-羟基乙酸共聚物负载吲哚菁绿的微球,延缓吲哚菁绿光降解,提高其光热稳定性。
方法:①采用乳液-溶剂蒸发法制备聚乳酸-羟基乙酸共聚物负载吲哚菁绿的微球,对其形貌、粒径分布、表面电荷、载药量和包封率进行表征。②将游离吲哚菁绿溶液与吲哚菁绿微球悬液在不同质量浓度下(0.6,0.8,1.0,1.2 g/L)经近红外光辐照5 min,考察溶液温度变化;将游离吲哚菁绿溶液与吲哚菁绿微球悬液在1.0 g/L质量浓度下未避光放置0,3,6,9 d,观察近红外光辐照5 min内的温度变化;将游离吲哚菁绿溶液与吲哚菁绿微球悬液在1.0 g/L质量浓度下进行4个开-关激光光照循环,考察溶液温度变化。③将舌鳞癌细胞系SCC-25接种于48孔板内,分8组培养:对照组、空白微球组、1.0 g/L游离吲哚菁绿组、1.0 g/L吲哚菁绿微球组、近红外光照组、空白微球+近红外光照组、1.0 g/L游离吲哚菁绿+近红外光照组和1.0 g/L吲哚菁绿微球+近红外光照组。处理12 h后,采用CCK-8法检测细胞活力。
结果与结论:①吲哚菁绿微球表面光滑,平均粒径为(2.54±0.29) μm,Zeta电位为-(20.2±1.58) mV,包封率和载药率分别为(69.24±1.29)%和(4.87±0.15)%;②游离吲哚菁绿与吲哚菁绿微球具有相似的光热转换能力,但增加激光辐照次数或未避光存放后,游离吲哚菁绿的光热转换能力较吲哚菁绿微球明显降低;③1.0 g/L游离吲哚菁绿+近红外光照组和1.0 g/L吲哚菁绿微球+近红外光照组的SCC-25细胞皱缩呈球型,该两组的细胞活力低于对照组(P < 0.001);④结果表明,吲哚菁绿微球具有高效的光热转换效率,明显延缓了吲哚菁绿的光漂白和光降解。

https://orcid.org/0000-0003-1038-8240 (范亚茹) 

中国组织工程研究杂志出版内容重点:生物材料;骨生物材料口腔生物材料纳米材料缓释材料材料相容性组织工程

关键词: 聚乳酸-羟基乙酸共聚物, 吲哚菁绿, 微球, 口腔鳞状细胞癌, 光热治疗, SSC-25细胞, 近红外光, 乳液-溶剂蒸发法

Abstract: BACKGROUND: Indocyanine green, an efficient photothermal conversion agent, can be used for photothermal therapy of oral squamous cell carcinoma, but it has some shortcomings such as water instability and photodegradation. Using a carrier to encapsulate indocyanine green to improve its stability was of great significance for exploring photothermal therapy of oral squamous cell carcinoma.  
OBJECTIVE: Indocyanine green encapsulated poly lactic acid-co-glycolic acid microspheres were fabricated to delay the photodegradation of indocyanine green and improve its photothermal stability. 
METHODS: (1) The indocyanine green encapsulated poly lactic acid-co-glycolic acid microspheres were prepared by emulsion-solvent evaporation method. The morphology, particle size distribution, surface charge, drug loading and encapsulation efficiency were characterized. (2) The free indocyanine green solution and the indocyanine green microsphere suspension were irradiated with near-infrared light at different mass concentrations (0.6, 0.8, 1.0, 1.2 g/L) for 5 minutes to investigate the temperature changes of the solutions. The free indocyanine green solution and the indocyanine green microsphere suspension were exposed to natural light for 0, 3, 6, and 9 days at a mass concentration of 1.0 g/L to observe the temperature changes within 5 minutes of near-infrared light irradiation. The free indocyanine green solution and the indocyanine green microsphere suspension were subjected to four on-off laser irradiation cycles at a mass concentration of 1.0 g/L to investigate the temperature changes of the solutions. (3) The tongue squamous cell carcinoma cell line SCC-25 was inoculated in a 48-well plate and cultured in eight groups: control group, blank microsphere group, 1.0 g/L free indocyanine green group, 1.0 g/L indocyanine green microsphere group, near-infrared light group, blank microsphere+near-infrared light group, 1.0 g/L free indocyanine green+near-infrared light group, and 1.0 g/L indocyanine green microsphere+near-infrared light group. After 12 hours of treatment, cell viability was detected by CCK-8 assay.  
RESULTS AND CONCLUSION: (1) The indocyanine green microspheres had smooth surfaces with particle sizes of (2.54±0.29) μm and zeta potential of −(20.2±1.58) mV. Encapsulation efficiency and loading efficiency were (69.24±1.29)% and (4.87±0.15)%, respectively. (2) Free indocyanine green and indocyanine green microspheres had similar photothermal conversion ability, but after increasing the number of laser irradiation or storage without light, the photothermal conversion ability of free indocyanine green obviously decreased compared with indocyanine green microspheres. (3) The SCC-25 cells in the 1.0 g/L free indocyanine green+near-infrared light group and the 1.0 g/L indocyanine green microsphere+near-infrared light group shrank to a spherical shape, and the cell viability of the two groups was lower than that of the control group (P < 0.001). (4) Indocyanine green microspheres possess efficient photothermal conversion ability and can obviously delay photobleaching and photodegradation of indocyanine green. 

Key words: poly lactic acid-co-glycolic acid, indocyanine green, microsphere, oral squamous cell carcinoma, photothermal therapy, SSC-25 cell, near-infrared, emulsion-solvent evaporation method

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