Early response evaluation of doxorubicin-nanoparticle-microbubble therapy in orthotopic hepatocellular carcinoma rat model using contrast-enhanced ultrasound and intravoxel incoherent motion-diffusion MRI

Abstract

To apply doxorubicin-loaded nanoparticle microbubble (Dox-NP-MB) therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) and investigate the utility of contrast-enhanced ultrasound (CEUS) and intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) in response evaluation. Methods: Twenty-eight N1S1 HCC model rats were treated with either Dox-NP-MB (Group [G] 1 [n=8]); doxorubicin (Dox) alone (G2, [n=7]); nanoparticle microbubbles (NP-MB) alone (G3, [n=7]; or saline (G4, control, [n=6]) on days 0 and 7 with sacrifice on day 11. IVIM-DWI and CEUS were performed before each treatment and before euthanasia. Efficacy was estimated by the percentage of tumor volume growth inhibition compared with control. Toxicity was assessed by body weight changes and blood tests. Post-treatment changes in IVIM-DWI and CEUS parameters were analyzed. Results: Tumor volume growth was inhibited by 48.4% and 90.2% in G1 and G2 compared to G4, respectively. Compared to G2, G1 had a significantly lower degree of body weight change (91.0% [88.5-97.0] vs. 88.0% [82.5-88.8], p <0.05) and leukopenia (1.75 × 10 3 cells/uL [1.53-2.77] vs. 1.20 × 10 3 cells/uL [0.89-1.51], p <0.05). After the first treatment, an increase in peak enhancement, wash-in rate, and wash-in perfusion index on CEUS was observed in G3 and G4 but suppressed in G1 and G2; apparent diffusion coefficients (ADC), true diffusion coefficients (D), and perfusion fractions (PF) significantly increased in G1 and G2 compared to baseline (p <0.05). Conclusion:Dox-NP-MB showed reduced Dox toxicity. Early changes in some CEUS and IVIM-DWI parameters correlated with therapeutic response.

Nano-drug delivery system for pancreatic cancer: A visualization and bibliometric analysis

“…The latest research by Meng et al reported that the optimized NPs with virus-mimic surface topology combined with low-frequency ultrasound microbubbles significantly enhanced the permeability of the biological barrier and enhanced the distribution of NPs in solid tumors ( Meng et al, 2021 ). In recent years, the combination of NDDS and ultrasound microbubbles has shown great potential in improving gene transfection efficiency in gene therapy ( Tay and Xu, 2017 ; Wang et al, 2022a ; Kida et al, 2022 ), and improving the efficacy of chemotherapy drugs on a variety of tumors including PC ( Gao et al, 2019 ; Lee et al, 2020 ; Liu et al, 2020 ; Yang et al, 2022a ; Ngamcherdtrakul et al, 2022 ; Schoen et al, 2022 ). However, it should be noted that the size and concentration of microbubbles and the total amount of gas contained in the liquid are important factors affecting NDDS mediated by ultrasound microbubbles ( Kida et al, 2022 ).…”

Multifunctional nanoplatforms application in the transcatheter chemoembolization against hepatocellular carcinoma

“…S1) [ 78 ]. Based on the unique advantages of ultrasound and nanotechnology, ultrasound nanomedicine has been regarded as a highly promising and valuable tumor-specific theragnostic methodology, which will pave a novel and efficient way for combating cancer [ 84 , 85 ].…”