Preclinical Therapeutic Evaluation of Lenvatinib-Eluting Microspheres for Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma.
Preclinical Therapeutic Evaluation of Lenvatinib-Eluting Microspheres for Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma.
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DOI：
10.1007/s00270-022-03242-8
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发表时间：
2022-12
影响因子：
2.9
通讯作者：
Kim, Dong-Hyun
中科院分区：
文献类型：
--
作者：
Pe, Jason;Choi, Bongseo;Choi, Hyunjun;Kwon, Soon Woo;Kim, Dong-Hyun
关键词：
评估乐伐替尼洗脱微球 (LEN-EM) 经导管动脉化疗栓塞 (LEN-TACE) 在肝细胞癌 (HCC) 大鼠模型中的临床前体内治疗反应。采用聚丙交酯乙交酯和氧化铁纳米颗粒通过双乳液法制备了磁共振成像（MRI）可见光LEN-EM。评估了 LEN-EM 的形态、LEN 加载/释放动力学和 MRI 对比效果。对于体内研究，N1S1 HCC 大鼠使用 LEN-EM 进行 LEN-TACE（LEN：2.4 mg/kg，n = 5）、全身 LEN（LEN：0.4 mg/kg，每天口服灌胃，持续 7 天，n = 5）、对照（动脉内 (IA) 盐水输注，n = 5）和非肿瘤对照（n = 3）。测量肿瘤大小变化两周。测量了各组之间的组织学、比较 LEN 血浆浓度、血液学标志物、肝脏概况和血清化学。通过优化乳液工艺制备平均粒径为 33 μm 的 LEN-EM。 LEN加载效率为58.7%。 LEN连续释放500小时。 LEN-TACE 在 MRI-T2* 图像中显示了所递送的 LEN-EM 周围的肿瘤组织。术后 2 周，与其他组相比，LEN-TACE 组的肿瘤体积缩小程度具有统计学意义。末端脱氧核苷酸转移酶 dUTP 缺口末端标记阳性细胞的定量数据证实，与对照组相比，LEN-TACE 组的癌细胞死亡增加。其他组织学、血液学标志物和肝脏特征显示 LEN-TACE 的副作用最小。使用 IA 递送 LEN-EM 的 LEN-TACE 在 HCC 大鼠动物模型中证明了有效的治疗效果。
To evaluate the preclinical in vivo therapeutic response of Lenvatinib-eluting microspheres (LEN-EM) transcatheter arterial chemoembolization (LEN-TACE) in an hepatocellular carcinoma (HCC) rat model. Magnetic resonance imaging (MRI) visible LEN-EM was fabricated with poly(lactide-co-glycolide) and iron oxide nanoparticles by a double-emulsion method. The morphology, LEN loading/release kinetics, and MRI contrast effect of LEN-EM were evaluated. For in vivo study, N1S1 HCC rats were treated with LEN-TACE (LEN: 2.4 mg/kg, n = 5) using LEN-EM, systemic LEN (LEN: 0.4 mg/kg, oral gavage daily for 7 days, n = 5), control (intra-arterial (IA) saline infusion, n = 5), and non-tumor control (n = 3). Tumor size changes were measured for 2 weeks. Histology, comparative LEN plasma concentration, hematologic markers, liver profile, and serum chemistry among the groups were measured. LEN-EM with 33 μm in average size was prepared in an optimized emulsion process. LEN loading efficiency was 58.7%. LEN was continuously released for 500 h. LEN-TACE showed the delivered LEN-EM surrounding tumor tissue in MRI-T2* images. The LEN-TACE group demonstrated a statistically significant larger tumor volume reduction compared to the other groups at 2 weeks post-procedure. Quantification data of Terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells confirmed increased cancer cell death in the LEN-TACE group compared to control groups. Additional histology, hematologic markers, and liver profiles showed minimal side effects of LEN-TACE. LEN-TACE using IA delivery of LEN-EM demonstrated an effective therapeutic efficacy in an HCC rat animal model.
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