Preparation of docetaxel‑loaded, glycyrrhetinic acid‑modified nanoparticles and their liver‑targeting and antitumor activity

Abstract

Liver cancer is one of the most common malignancies worldwide and poses a serious threat to human health. The most important treatment method, liver cancer chemotherapy, is limited due to its high toxicity and poor specificity. Targeted drug delivery systems have emerged as novel therapeutic strategies that deliver precise, substantial drug doses to target sites via targeting vectors and enhance the therapeutic efficacy. In the present study, glycyrrhetinic acid-modified hyaluronic acid (GA-HA) was used as a carrier for the model drug docetaxel (DTX) to prepare DTX-loaded GA-HA nanoparticles (DTX/GA-HA-NPs). The results indicated that the DTX/GA-HA-NPs exhibited high monodispersity (particle dispersity index, 0.209±0.116) and desirable particle size (208.73±5.0 nm) and zeta potential (-27.83±3.14 mV). The drug loading capacity and encapsulation efficiency of the NPs were 12.59±0.68 and 85.38±4.62%, respectively. Furthermore, it was determined that FITC-GA-HA was taken up by cells and distributed in the cytoplasm. DTX and DTX/GA-HA (just the DTX delivered by the nanoparticle) aggregated and altered the structure of cellular microtubules. Compared with DTX alone, DTX/GA-HA-NPs had a stronger inhibitory effect on HepG2 cell proliferation and promoted apoptosis of HepG2 cells. All experimental results indicated that DTX/GA-HA-NPs were successfully prepared and had liver-targeting and antitumor activities in vitro , which provided a foundation for future in vivo studies of the antitumor effects of DTX/GA-HA-NPs.

Oncopreventive and oncotherapeutic potential of licorice triterpenoid compound glycyrrhizin and its derivatives: Molecular insights

“…Different types of nano-formulations are being developed, such as the GA-DTX-NGO system, which delivers the chemotherapeutic agent docetaxel (DTX) in nanomaterial composed of GA and nanographene oxide (NGO) to treat liver cancer [164] . Another formulation is DTX/GA-HA-NPs, in which glycyrrhetinic acid-modified hyaluronic acid (GA-HA) is used in combination with the drug DTX [165] . A recent review highlighted the drug carrier potential of GZA and18β-GA in liver cancer [166] .…”

Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy

“…In addition, HA can actively target the surfaces of cancer cells, such as HCC cells, by binding the CD44 receptor. Xue and coworkers tested in vitro GA-modified HA NPs as carriers for the model drug docetaxel (DTX) [ 47 ]. DTX is known to bind the β-tubulin subunit of microtubulin and to induce microtubule stabilization and prevent its de-polymerization [ 86 ] but is also able to enhance the polymerization of cellular tubulin by binding α-tubulin.…”

Chemotherapeutic nanomaterials in tumor boundary delineation: Prospects for effective tumor treatment

“…Moreover, the liver tumor boundary was adequately mapped in H&E images enabled by DOX-mediated necrosis. Also, glycyrrhetinic acid-modified hyaluronic acid nanoparticles that were loaded with docetaxel showed substantial liver tumor chemotherapy and boundary mapping 139 . The glycyrrhetinic acid-based nanoparticles were modified with hyaluronic acid to obtain the monodispersed nanocarrier of 208 nm size and surface charge of ‒27 mV for conveying docetaxel to liver tumor site.…”