Zhejiang Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, 310005, Zhejiang, China.
Department of Nuclear Medicine, Shanghai Changhai Hospital, Shanghai, 200433, China.
J Nanobiotechnology. 2023 Aug 19;21(1):278. doi: 10.1186/s12951-023-02032-9.
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 (I/I-SFMS) after embolization of rat hepatic artery was dynamically recorded by SPECT. Transhepatic arterial radioembolization (TARE) with I-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 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 I-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 I-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.
丝素蛋白（SF）具有优异的物理化学和生物医学性能，适合开发生物医学材料。本研究定制了两种粒径范围的丝素蛋白微球（SFMS），然后负载金纳米粒子或阿霉素，以评估载药和释药性能。通过大鼠尾动脉和兔耳动脉评估栓塞效率，通过 SPECT 动态记录碘标记丝素微球（I/I-SFMS）栓塞大鼠肝动脉后的体内分布。采用碘标记丝素微球（I-SFMS）对肝癌大鼠模型进行经肝动脉放射性栓塞（TARE）治疗。用 SPECT/CT 记录选择性内放射治疗的全过程，用 F-FDG PET/CT 评估治疗效果。最后，记录酶降解情况，并对亚微米丝素的粒径清除进行评价。
SFMS 表面光滑，形状规则，微球内外均有遍及的孔，粒径适合 TAE。载药功能化的 SFMS 具有化疗或放射增敏作用，持续释放阿霉素或更致命的辐射，在治疗 HUH-7 细胞时证明了增强的治疗效果。用于动脉栓塞时，SFMS 有效阻断了血液供应；当 I-SFMS 作为栓塞剂时，良好的标记稳定性和栓塞性能保证了原位肝肿瘤治疗的良好疗效。在 TARE 后第 5 天，每只小鼠给予 37MBq/3mg I-SFMS，肿瘤活性迅速被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，对于可生物降解的 SFMS 碎片，较小的 SF（<800nm）在胃肠道中代谢，并通过泌尿系统排出，而 SF（>800nm）在 72 小时内进入肝脏进行进一步代谢。
SFMS 作为肝癌可降解 TARE 剂的可行性得到了初步证实，为其提供了多种治疗潜力。
