Multifunctional Drug-Loaded Phase-Change Nanoparticles Inhibit the Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Affecting the Activity of Activated Hepatic Stellate Cells

• Published in: BioMed research international Vol. 2022; pp. 6441179 - 18
• Main Authors: Zou, Xiaomeng, Li, Tiantian, Mao, Yingxuan, Zhu, Mingwei, Chen, Xi, Niu, Jiamei, Dong, Tianxiu, Jiang, Jian, Yang, Xiuhua
• Format: Journal Article
• Language: English
• Published: United States Hindawi 12-11-2022; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Apoptosis; Assaying; Biocompatibility; Biosafety; Body weight; Cancer; Cancer therapies; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Care and treatment; Cell proliferation; Cholecystokinin; Contrast agents; Diagnosis; Drug delivery systems; Drug therapy; Drugs; Efficiency; Epithelial-Mesenchymal Transition; Extracellular matrix; Fibroblasts; Health aspects; Hepatic Stellate Cells - pathology; Hepatocellular carcinoma; Hepatoma; Hydration; Irradiation; Liposomes; Liver; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Load distribution; Loading rate; Mesenchyme; Metastases; Metastasis; Mice; Mice, Nude; Nanoparticles; Nanostructured materials; Pancreatic cancer; Particle size; Permeability; Phase change; Phase transitions; Polyethylene glycol; Radiation; Signal transduction; Smad2 protein; Stellate cells; Thin films; Toxicity; Ultrasonic imaging; Ultrasound; Vaporization; Wound healing; Zeta potential; China; United States > US
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2022/6441179

Objectives. Preparation of a multifunctional drug-loaded phase-change nanoparticle (NP), pirfenidone perfluoropentane liposome NPs (PPL NPs), and combined with low-intensity focused ultrasound (LIFU) to influence epithelial mesenchymal transition (EMT) for hepatocellular carcinoma (HCC) by inhibiting the activity of activated Hepatic Stellate Cells (a-HSCs). Methods. PPL NPs were prepared by the thin film dispersion method. The appearance, particle size, zeta potential, encapsulation efficiency, drug loading rate, drug release in vitro, and stability of PPL NPs were tested. The role of a-HSCs in HCC metastasis was studied by CCK-8, colony formation assay, apoptosis, cellular uptake assay, wound healing assay, and Transwell assay. Western blot was used to detect the related protein expression levels. In vitro and vivo, the acoustic droplet vaporization (ADV) of PPL NPs was tested at different times and LIFU intensities. Biosafety of the PPL NPs was assessed by measuring nude mouse body weight and hematoxylin and eosin (H&E) staining. Results. The results showed that the PPL NPs had good biosafety, with an average particle size of 346.6±62.21 nm and an average zeta potential of -15.23 mV. When the LIFU power is 2.4 W/cm2, it can improve the permeability of cells, further promote the uptake of drugs by cells, and improve the toxicity of drugs. In vitro experiments showed that PPL NPs could inhibit the proliferation of a-HSCs cells, thereby affecting the metastasis of HCC, and were related to the TGFβ-Smad2/3-Snail signaling pathway. Both in vivo and in vitro PPL NPs enhanced ultrasound imaging by LIFU-triggered ADV. Conclusion. The PPL NPs designed and prepared in this study combined with LIFU irradiation could significantly alter the EMT of HCC by inhibiting LX2. Clinically, PPL NPs will also be considered a promising contrast agent due to their ultrasound imaging capabilities.