Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, People's Republic of China.
Department of Ultrasound, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, People's Republic of China.
Int J Nanomedicine. 2020 Feb 28;15:1373-1385. doi: 10.2147/IJN.S233989. eCollection 2020.
Photothermal therapy (PTT) has great potential application in the treatment of tumors. However, due to the low penetration of near-infrared light (NIR) and the low concentration of nanomaterials in the tumor site, the application of PTT has been limited.
The objective of this study was to investigate the therapeutic effect of transcatheter intra-arterial infusion of lecithin-modified Bi nanoparticles (Bi-Ln NPs) combined with interventional PTT (IPTT) on hepatocellular carcinoma.
Bi-Ln NPs were prepared by emulsifying the hydrophobic Bi nanoparticles and lecithin, and the photothermal conversion and cytotoxicity of Bi-Ln NPs were then measured by infrared imaging and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, respectively. Twenty-four VX2 hepatic carcinoma rabbits were randomly divided into four groups. Rabbits in group A received Bi-Ln NPs by intra-arterial infusion and NIR laser treatment (IA Bi-Ln NPs + Laser), group B received Bi-Ln NPs by intravenous infusion and NIR laser treatment (IV Bi-Ln NPs + Laser), group C received PBS (phosphate buffer saline) via intra-arterial infusion with NIR laser treatment (IA PBS + Laser), group D received PBS via intra-arterial infusion (IA PBS). Transcatheter intra-arterial infusion was conducted by superselective intubation under digital subtraction angiography (DSA) guidance. IPTT was performed by introducing an NIR optical fiber access to the rabbit VX2 hepatic carcinoma under real-time ultrasound guidance. Magnetic resonance imaging (MRI) was performed to evaluate the tumor size. Hematoxylin and eosin (H&E) stain and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were conducted 7 days after treatment to evaluate the necrosis rate and viability of tumor, respectively.
The Bi-Ln NPs have the advantages of good biological compatibility and high photothermal conversion efficiency. Minimally invasive transcatheter intra-arterial infusion can markedly increase the concentration of Bi-Ln NPs in tumor tissues. IPTT can contribute to the significant improvement in the photothermal efficiency of Bi-Ln NPs. Compared to other groups, the group of IA Bi-Ln NPs + Laser showed a significantly higher tumor inhibition rate (TIR) of 93.38 ± 19.57%, a higher tumor necrosis rate of 83.12 ± 8.02%, and a higher apoptosis rate of (43.26 ± 10.65%) after treatment.
Transcatheter intra-arterial infusion combined with interventional PTT (IPTT) is safe and effective in eradicating tumor cells and inhibiting tumor growth and may provide a novel and valuable choice for the treatment of hepatocellular carcinoma in the future.
光热疗法（PTT）在肿瘤治疗中有很大的应用潜力。然而，由于近红外光（NIR）的低穿透性和肿瘤部位纳米材料的低浓度，PTT 的应用受到了限制。
本研究旨在探讨经导管肝动脉内输注磷脂酰胆碱修饰的 Bi 纳米粒子（Bi-Ln NPs）联合介入性 PTT（IPTT）治疗肝细胞癌的疗效。
通过乳化疏水性 Bi 纳米粒子和磷脂酰胆碱制备 Bi-Ln NPs，分别通过红外成像和 MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐）测定 Bi-Ln NPs 的光热转换和细胞毒性。24 只 VX2 肝癌兔随机分为四组。A 组兔经肝动脉内输注 Bi-Ln NPs 并接受近红外激光治疗（IA Bi-Ln NPs + Laser），B 组兔经静脉内输注 Bi-Ln NPs 并接受近红外激光治疗（IV Bi-Ln NPs + Laser），C 组兔经肝动脉内输注磷酸盐缓冲盐水（PBS）并接受近红外激光治疗（IA PBS + Laser），D 组兔经肝动脉内输注 PBS（IA PBS）。经数字减影血管造影（DSA）引导下超选择性插管进行经导管肝动脉内输注。在实时超声引导下将近红外光纤引入兔 VX2 肝癌内进行 IPTT。磁共振成像（MRI）用于评估肿瘤大小。治疗后 7 天进行苏木精和伊红（H&E）染色和末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL），分别评估肿瘤坏死率和活力。
Bi-Ln NPs 具有良好的生物相容性和高光热转换效率的优点。微创经导管肝动脉内输注可显著增加肿瘤组织中 Bi-Ln NPs 的浓度。IPTT 有助于显著提高 Bi-Ln NPs 的光热效率。与其他组相比，IA Bi-Ln NPs + Laser 组的肿瘤抑制率（TIR）为 93.38 ± 19.57%，肿瘤坏死率为 83.12 ± 8.02%，凋亡率为（43.26 ± 10.65%）更高。
经导管肝动脉内输注联合介入性 PTT（IPTT）在杀灭肿瘤细胞、抑制肿瘤生长方面是安全有效的，可能为未来肝细胞癌的治疗提供一种新的有价值的选择。
