研究动态
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基于丝素纤维蛋白的栓塞剂,用于可对多种疾病进行肝门动脉栓塞治疗。

Silk fibroin-based embolic agent for transhepatic artery embolization with multiple therapeutic potentials.

发表日期:2023 Aug 19
作者: Linlin Shi, Danni Li, Qianqian Tong, Guorong Jia, Xiaohong Li, Lan Zhang, Qingqing Han, Rou Li, Changjing Zuo, Wei Zhang, Xiao Li
来源: JOURNAL OF NANOBIOTECHNOLOGY

摘要:

卓越的物理化学和生物医学特性使得丝素蛋白(SF)适用于生物医学材料的开发。本研究中,通过定制两种尺寸范围的丝素蛋白微球(SFMS),并携带金纳米粒子或柔红霉素(doxorubicin)来评估药物的负载和释放性能。在大鼠尾动脉和兔耳动脉中评估了栓塞效率,并通过SPECT动态记录了125I/131I-SFMS栓塞大鼠肝动脉后的体内分布情况。利用131I-SFMS对患有肝癌的大鼠模型进行经肝经管放射治疗(TARE)。使用SPECT/CT全程记录了选择性内放射治疗的过程,并通过18F-FDG PET/CT评估了治疗效果。最后记录了酶降解过程,并通过颗粒大小对亚微米丝素蛋白的清除情况进行评估。 SFMS具有光滑的表面和规则的形状,在表面和微球内部具有广泛的孔隙,并且大小范围适合TAE。药物负载功能化SFMS进行化疗或放射增敏,并且在治疗HUH-7细胞时证明了持久的柔红霉素释放或更具毒性的辐射。对于动脉栓塞,SFMS有效阻断了血液供应。当131I-SFMS充当栓塞剂时,良好的标记稳定性和栓塞性能保证了治疗原位肝肿瘤的有利效果。在用每只小鼠37 MBq/3 mg 131I-SFMS进行TARE治疗后的第5天,肿瘤活性迅速抑制到与周围正常肝脏相当的葡萄糖代谢水平。更重要的是,对于可降解的SFMS碎片,尺寸较小的SF (<800 nm)在胃肠道中代谢,并通过尿液系统排出,而尺寸较大的SF (>800 nm)在72小时内进入肝脏进行进一步代谢。 SFMS作为可降解的TARE治疗剂对于肝癌的可行性通过提供多种治疗潜力得到初步证明。 © 2023. BioMed Central Ltd., part of Springer Nature.
The excellent physicochemical and biomedical properties make silk fibroin (SF) suitable for the development of biomedical materials. In this research, the silk fibroin microspheres (SFMS) were customized in two size ranges, and then carried gold nanoparticles or doxorubicin to evaluate the performance of drug loading and releasing. Embolization efficiency was evaluated in rat caudal artery and rabbit auricular artery, and the in vivo distribution of iodinated SFMS (125I/131I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with 131I-SFMS was performed on rat models with liver cancer. The whole procedure of selective internal radiation was recorded with SPECT/CT, and the therapeutic effects were evaluated with 18 F-FDG PET/CT. Lastly, the enzymatic degradation was recorded and followed with the evaluation of particle size on clearance of sub-micron silk fibroin.SFMS were of smooth surface and regular shape with pervasive pores on the surface and inside the microspheres, and of suitable size range for TAE. Drug-loading functionalized SFMS with chemotherapy or radio-sensitization, and the enhanced therapeutic effects were proved in treating HUH-7 cells as lasting doxorubicin release or more lethal radiation. For artery embolization, SFMS effectively blocked the blood supply; when 131I-SFMS serving as the embolic agent, the good labeling stability and embolization performance guaranteed the favorable therapeutic effects in treating in situ liver tumor. At the 5th day post TARE with 37 MBq/3 mg 131I-SFMS per mice, tumor activity was quickly inhibited to a comparable glucose metabolism level with surrounding normal liver. More importantly, for the fragments of biodegradable SFMS, smaller sized SF (< 800 nm) metabolized in gastrointestinal tract and excreted by the urinary system, while SF (> 800 nm) entered the liver within 72 h for further metabolism.The feasibility of SFMS as degradable TARE agent for liver cancer was primarily proved as providing multiple therapeutic potentials.© 2023. BioMed Central Ltd., part of Springer Nature.