In vitro and in vivo antitumor effects of lupeol-loaded galactosylated liposomes

Abstract

Lupeol liposomes, modified with Gal-PEG-DSPE, were developed following a thin-film dispersion method. Then, the morphology, physicochemical properties, and in vitro release properties of those liposomes were investigated. The scanning electron microscopic images showed that most of the liposomes were spherical particles; they were similar in size and uniformly dispersed. Both lupeol liposomes and Gal-lupeol liposomes exhibited an average particle size of about 100 nm. The encapsulation efficiency was greater than 85%. The encapsulation efficiency of lupeol liposome and Gal-lupeol liposome, stored with 15% sucrose as glycoprotein for 6 months, was higher than 80%; although the particle size increased, they remained within 200 nm. The cell-uptake study demonstrated that the Gal-lupeol-liposome uptake efficiency was the highest in HepG2 cells. The HepG2 cells treated with the Gal-lupeol liposomes had higher apoptotic efficiency than the lupeol liposome and free lupeol. After HepG2 cells were treated with Gal-lupeol liposome, the expressions of AKT/mTOR-related proteins (p-AKT308 and p-AKT473) were also significantly reduced than the lupeol-liposome and free lupeol group. The in vivo targeting studies showed that Gal-NR-L exhibited liver-targeting effects on FVB mice. The pharmacodynamic study was performed by transfecting AKT and c-MET via the high-pressure tail vein of FVB mice. After Gal-lupeol-L administration, the liver index and liver weight of mice were less than those non-targeted group. The histopathological study showed that the lobular structure in the mice liver was clearer, the vacuoles were more obvious, and the cytoplasm was more abundant after Gal-lupeol-L administration. Also, the qRT-PCR study showed that AFP, GPC3, and EpCAM mRNA expression levels were significantly lower than those non-targeted lupeol-liposomes.

Galactose-decorated liver tumor-specific nanoliposomes incorporating selective BRD4-targeted PROTAC for hepatocellular carcinoma therapy

“…This leads to higher cellular uptake of galactose conjugated nanocarriers and subsequent drug delivery of encapsulated cargos in hepatocellular carcinoma. Zhang et al (2021), demonstrated the successful uptake of lupeol-loaded galactosylated liposomes by HepG2 cells, followed by efficacious in vitro and in vivo antitumor effects in the HCC xenograft model (Zhang et al, 2021). As previously shown by Nair et al (2019), gemcitabine-loaded galactosylated chitosan nanoparticles resulted in liver tumor-specific delivery and enhanced the anti-HCC efficacy of gemcitabine in vivo (Nair et al, 2019).…”

“…This leads to higher cellular uptake of galactose conjugated nanocarriers and subsequent drug delivery of encapsulated cargos in hepatocellular carcinoma. Zhang et al. (2021) , demonstrated the successful uptake of lupeol-loaded galactosylated liposomes by HepG2 cells, followed by efficacious in vitro and in vivo antitumor effects in the HCC xenograft model ( Zhang et al., 2021 ).…”

“… Zhang et al. (2021) , demonstrated the successful uptake of lupeol-loaded galactosylated liposomes by HepG2 cells, followed by efficacious in vitro and in vivo antitumor effects in the HCC xenograft model ( Zhang et al., 2021 ). As previously shown by Nair et al.…”

The Optimized Delivery of Triterpenes by Liposomal Nanoformulations: Overcoming the Challenges

“…In vivo tests on wild-type FVB/N mice emphasized the liver-targeted delivery of GAL-L; as a result, the liver index as well as the liver weight of the respective treated mice displayed lower values compared to the non-targeted group. Histopathological analysis revealed that the GAL-L-treated mice had a clearer liver lobular structure with more obvious vacuoles and more abundant cytoplasm; in addition, liver cancer markers such as AFP, GPC3, and EpCAM mRNA exhibited lower expression levels compared to non-targeted lupeol-loaded liposomes [289].…”

In vitro and in vivo Evaluation of a Novel Estrogen-Targeted PEGylated Oxaliplatin Liposome for Gastric Cancer

“…Recently, researchers have focused on tumor-targeted liposomal delivery system. Lactoferrin, 20 galactose 21 and glycyrrhetinic acid, 22 , 23 and so on were used to modify liposomes to target drugs into the tumor tissue more effectively. Estrogen receptors belong to the nuclear receptor protein family 24 involved in various physiological processes such as cell growth, reproduction, development, and differentiation.…”