Targeted Delivery of Paclitaxel in Liver Cancer Using Hyaluronic Acid Functionalized Mesoporous Hollow Alumina Nanoparticles

Abstract

Hyaluronic acid functionalized mesoporous hollow alumina nanoparticles (HMHA) were used as a tumor-targeted delivery carrier for liver cancer therapy. Paclitaxel (PAC) incorporated in the carrier by the adsorption method was analyzed by X-ray diffraction and differential scanning calorimetry. PAC was found to be in an amorphous state. The hyaluronic acid coated on the surface of mesoporous hollow alumina nanoparticles (MHA) regulated the drug release rate and the loaded samples obtained a sustained drug release. In vitro experiments demonstrated that paclitaxel-hyaluronic acid functionalized mesoporous hollow alumina nanoparticles (PAC-HMHA) had a high cellular uptake, which increased the drug level in tumor tissues and was beneficial to promote apoptosis. An in vivo tumor inhibition rate study demonstrated that PAC-HMHA (64.633 ± 4.389%) had a better antitumor effect than that of paclitaxel-mesoporous alumina nanoparticles (PAC-MHA, 56.019 ± 6.207%) and pure PAC (25.593 ± 4.115%). Therefore it can be concluded that PAC-HMHA are a prospective tumor-targeted delivery medium and can be useful for future cancer therapy.

New Small-Molecule Glycoconjugates of Docetaxel and GalNAc for Targeted Delivery to Hepatocellular Carcinoma

“…However, DTX is still not applicable for HCC therapy because it showed insufficient efficacy and safety in stage II clinical trials, despite its universal mechanism of action and impressive in vitro test results with HCC cell lines. − Targeted delivery is a modern and promising way to increase the selectivity of action and the effectiveness of drug agents. To date, numerous attempts to create systems of targeted delivery of taxanes for treating HCC using nanoparticles and various formulations are known. − However, similar high-molecular-weight delivery systems have limited applicability because of drawbacks such as difficult permeability of cell membranes and blood vessel walls, immune response, instability in blood plasma, problems with solubility, etc . Moreover, most of such delivery systems rely on passive transport, while active transport by receptor-mediated endocytosis could facilitate the penetration of drugs through the cell membrane.…”

The pathogenesis of liver cancer and the therapeutic potential of bioactive substances

“…This research team also confirmed that the filamentous structure promoting cell adhesion was almost completely inhibited when the tumor cells were treated with a 9 nM concentration of EPS11, and that tumor cell migration was reduced under the same conditions. At the same time, mRNA Spectinabilin (1) ↓Protein levels of cyclin B1 and cdc2; ↓Cell cycle in G2/M phase of SMMC7721 and HepG2 cells Human hepatoma cell line HepG2 Gao et al (2019b) Frontiers in Pharmacology frontiersin.org and protein levels for CD99 (a glycosylated transmembrane protein) decreased in a dose-dependent manner, further confirming the anti-cell migration effects of EPS11 . Surprisingly, this research group also isolated and purified EPS364 from Vibrio alginolyticus 364, and not only confirmed that EPS364 showed anti-tumor effects that were similar to those of EPS11, but also that it possibly downregulated the fibroblast growth factor 19 (FGF19)-fibroblast growth factor receptor 4 (FGFR4) signal axis.…”

Targeting Strategies for Enhancing Paclitaxel Specificity in Chemotherapy

“…Anti-MDR drugs (such as apatinib) co-delivered together with PTX have shown a favorable efficacy enhancement ( Zhang et al, 2020 ). It was found that HA-functionalized vehicles with a PTX payload notably suppressed tumor invasion, migration, and proliferation, including micelles (HA-CA), selenium NPs (HA-Se@PTX), and mesoporous hollow alumina NPs (PAC-HMHA) ( Thomas et al, 2015 ; Gao et al, 2019 ; Zou et al, 2019 ; Tang Y. et al, 2020 ). Previous studies have shown that HA-coated nanostructured lipids delivering PTX remarkably prolonged blood retention and tumor accumulation compared with Taxol ( Yang et al, 2013 ).…”