Multilayer-Coated Liquid Crystalline Nanoparticles for Effective Sorafenib Delivery to Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma is one of the most common cancers in adults and develops due to activation of oncogenes and inactivation of tumor suppressor genes. Sorafenib (SF) is a U.S. Food and Drug Administration (FDA) approved drug for the treatment of hepatocellular carcinoma. However, its clinical use is limited by its poor aqueous solubility and undesirable side effects. Monoolein-based liquid crystalline nanoparticles (LCN) are self-assembled structures that have been determined as promising drug-delivery vehicles. Therefore, the main aim of this study was to prepare layer-by-layer (LbL) polymer-assembled SF-loaded LCNs (LbL-LCN/SF) for effective delivery of SF to hepatocellular carcinoma. Results revealed that LbL-LCN/SF presented optimum particle size (∼165 nm) and polydispersity index (PDI, ∼0.14) with appropriate polymer layer assembly confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Furthermore, LbL-LCN/SF effectively controlled burst release and exhibited pH-sensitive release of SF, thereby increasing drug release in the acidic microenvironment of tumor cells. Compared to free SF and bare LCN, the hemolytic activity of LbL-LCN/SF was significantly reduced (p<0.01). Interestingly, LbL-LCN/SF was more cytotoxic to HepG2 cells than the free drug was. Additionally, high cellular uptake and greater apoptotic effects of LbL-LCN/SF in HepG2 cells indicates superior antitumor effects. Therefore, LbL-LCN/SF is a potentially effective formulation for hepatocellular carcinoma.

Silver Nanoparticles Induce HePG-2 Cells Apoptosis Through ROS-Mediated Signaling Pathways

“…Meanwhile, owing to its poor sensitivity to chemotherapeutic agents, high metastatic potential, and resistance to traditional drugs, it is dismal to the overall prognosis of patients with HCC. Thus, it is imperative to develop efficient chemotherapy that has become the great challenge in clinical treatment [5,6]. In addition, most of current anticancer agents usually have short half-life in the blood circulation and poor aqueous solubility, which hampers therapeutic efficacy of chemotherapy [7,8].…”

Polyethylenimine-functionalized silver nanoparticle-based co-delivery of paclitaxel to induce HepG2 cell apoptosis

“…4,5 Meanwhile, as most cases with HCC are metastatic or advanced at the time of diagnosis, the local therapies including liver transplantation and surgical excision are unsuitable. 6,7 Furthermore, chemotherapeutic is generally ineffective against advanced HCC, which has high metastatic potential. 8 Finally, most conventional cancer therapeutics have a relatively short half-life and poor permeability, which may influence curative effect.…”

Easy on-demand self-assembly of lateral nanodimensional hybrid graphene oxide flakes for near-infrared-induced chemothermal therapy

“…Lysosomes, which exist at pH 4.5-5.0, could assist in DOX release inside the cells for targeted therapy. 39 Quantitative cellular uptake of nGO@DOX-cPEG flakes was performed using fluorescence-activated cell sorting (Figure 4c). In all three cell lines, nGO@DOX-cPEG flakes were uptaken in a concentration-and time-dependent manner.…”