Preparation and pharmacokinetics of glycyrrhetinic acid and cell transmembrane peptides modified with liposomes for liver targeted-delivery

Abstract

The article presents a hepatocellular carcinoma cell surface-specific ligand glycyrrhetinic acid (GA) and cell-penetrating peptide (TAT) with good cell membrane penetration to modify the anti-tumor drug pingyangmycin (PYM) liver delivery system, which achieve targeted delivery of drugs and improve anti-tumor efficiency. In this study, we synthesized the pingyangmycin liposome modified by glycyrrhetinic acid and cell penetrating peptide(GA-TAT-PYM-L) and evaluated the anti-tumor effect of GA-TAT-PYM-L in vitro. Using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylte-trazolium bromidecell proliferation method, GA-TAT-PYM-L had a stronger inhibitory effect on HepG2 cells than the free drug PYM at the same concentration. Acridine orange-ethidium bromide staining assays showed that GA-TAT-PYM-L had stronger apoptosis promotion effects on HepG2 cells in comparison to PYM. Pharmacokinetic studies indicated that, compared with PYM, GA-TAT-PYM-L enhanced mean residence time (MRT0–∞) and area under curve (AUC0–∞) by about 2.79-fold and 2.45-fold. The T 1/2 was prolonged to 140.23 ± 14.13 min. Tissue distribution results showed that the PYM concentrations in livers from the GA-TAT-PYM-L group were always higher than other tissues at each monitoring period after 5 min, indicating that GA-TAT-PYM-L can achieve liver targeting.

The application strategy of liposomes in organ targeting therapy

“…This allowed the delivery of Gefitinib (Gefi) encapsulated inside the liposomes, achieving therapeutic effects in hepatocellular carcinoma (Figure 2b) (Deepak et al, 2023). Li et al utilized liposomes with surface modification of glycyrrhetinic acid (GA) and a cell penetrating peptide to load the anti‐tumor drug Pingyangmycin (PYM), achieving hepatocyte surface targeting in liver cancer cells and increasing intracellular drug content (L. Li, Chen, et al, 2022). Additionally, agarose‐based ligands and FZD1 antibodies were also modified on the surface of liposomes to efficiently deliver drugs to the liver (Figure 2c) (Dhawan et al, 2022; Negro et al, 2023).…”

Four Ounces Can Move a Thousand Pounds: The Enormous Value of Nanomaterials in Tumor Immunotherapy

“…To further enhance the immunotherapeutic effect of nanomedicines against cancer cells, researchers have begun to modify some specific ligands on tumor cell membranes to enhance their function. [ 166 ] For example, Liu et al. [ 167 ] modified tumor cell membranes with mannose and wrapped them with the immune adjuvant R837 to obtain particles with a size of ≈160 nm, NP‐R@M‐M.…”

“…To further enhance the immunotherapeutic effect of nanomedicines against cancer cells, researchers have begun to modify some specific ligands on tumor cell membranes to enhance their function. [166] For example, Liu et al [167] modified tumor cell membranes with mannose and wrapped them with the immune adjuvant R837 to obtain particles with a size of ≈160 nm, NP-R@M-M. Antigens on the surfaces of tumor cell membranes target cancer cells. At the same time, mannose can specifically bind to DC cells and, together with R837, promote the body's production of a tumor-specific immune response against the tumor.…”