<p>Transcatheter Intra-Arterial Infusion Combined with Interventional Photothermal Therapy for the Treatment of Hepatocellular Carcinoma</p>

Abstract

Background: 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. Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

Doxorubicin-Loaded UiO-66/Bi2S3 Nanocomposite-Enhanced Synergistic Transarterial Chemoembolization and Photothermal Therapy against Hepatocellular Carcinoma

“…23 What is more, they always failed to achieve pHresponsive drug release and photothermal therapy simultaneously in TACE. [19][20][21][22]24 Therefore, new effective nanotechnologies are urgently required to enhance the TACE outcome.…”

“…25−27 Additionally, PTT has been extensively studied for cancer treatment and proven to be a good supplement to TACE. [19][20][21][22]24 Hyperthermia produced in PTT has a potent chemo-sensitizing effect, and incorporation of PTT as an additional treatment modality into chemotherapy displays great potential to overcome the chemoresistance of HCC. 28−30 Given all this, we proposed an innovative strategy to overcome the obstructions in TACE: synthesizing UiO-66/ Bi 2 S 3 , a kind of MOF-based composite, using a simple one-step solvothermal method.…”

“…First, the elimination of cancer cells by TACE is always incomplete because HCC also derives a small portion of blood supply from the extrahepatic artery. − Second, there are deficiencies in controlled drug release by using endogenous or exogenous stimuli in the tumor region. − Third, commonly used therapeutic agents are inevitably delivered to normal liver parenchyma, and this off-target effect leads to post-TACE liver dysfunction. , Therefore, it is urgent to develop a novel drug-delivery system and introduce additional treatment modality to enhance the TACE efficiency. The innovative application of introducing multifunctional nanomaterials into TACE provides a new way to overcome these obstacles. ,− With drug-delivery advantage, pH-responsive property or photothermal ability, nanomaterials were developed as chemotherapeutic transporters as well as the photothermal agents in TACE . However, for these nanosystems, the preparation procedure always suffered from a tedious synthetic process and strict reaction conditions. ,− Moreover, most of these research studies used VX2 tumor-bearing rabbits as the animal model, ,− and the primary shortcoming of this model was that the tumor was not pathologically similar to human HCC and the disease state can not mimic it .…”

Circular RNA Circ-0003006 Promotes Hepatocellular Carcinoma Proliferation and Metastasis Through Sponging miR-542-3p and Regulating HIF-1A

“…Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the second leading cause of tumor-related death. 1,2 In recent years, researchers have made significant progress in the treatment of hepatocellular carcinoma (HCC), including liver cancer resection, 3 liver transplantation, 3,4 radiofrequency ablation, 5 interventional therapy (chemotherapy and embolization), 6 and comprehensive treatment of targeted drugs. 7 Surgical resection is the best treatment of hepatocellular carcinoma (HCC), but because of hepatocellular carcinoma (HCC) onset conceals, early and no apparent symptoms.…”

Multifunctional CuBiS2 Nanoparticles for Computed Tomography Guided Photothermal Therapy in Preventing Arterial Restenosis After Endovascular Treatment

“…With the advantages above and novel nanoparticles being developed (such as modified/decorated metal-organic framework based nanomaterial), nanotech PTT has been shown to be greatly applied in the anti-tumor theranostics, cardiovascular diseases and nervous system diseases, etc. (Shan et al, 2018;Luo et al, 2019;Wang et al, 2019;Pan et al, 2020;Zhou et al, 2020). Using ZD2-engineered gold nanostar@ metaloragnic framework nanoprobes, it has been reported that the nanoprobes based PTT was efficient in treating triple-negative breast cancer with good magnetic resonance imaging property (Zhang et al, 2018).…”