Lactosylated Albumin Nanoparticles: Potential Drug Nanovehicles with Selective Targeting Toward an In Vitro Model of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) ranks fifth in occurrence and second in mortality of all cancers. The development of effective therapies for HCC is urgently needed. Anticancer drugs targeted to the liver-specific asialoglycoprotein receptors (ASGPRs) are viewed as a promising potential treatment for HCC. ASGPRs facilitate the recognition and endocytosis of molecules, and possibly vehicles with galactose end groups, by the liver. In this study, bovine serum albumin (BSA) was conjugated with lactose using a thermal treatment. The formation of lactosylated BSA (BSA-Lac) was confirmed by a change of the chemical structure, increased molecular mass, and Ricinus communis lectin recognition. Subsequently, the low-crosslinking BSA-Lac nanoparticles (LC BSA-Lac NPs) and high-crosslinking BSA-Lac nanoparticles (HC BSA-Lac NPs) were synthesized. These nanoparticles presented spherical shapes with a size distribution of 560 ± 18.0 nm and 539 ± 9.0 nm, as well as an estimated surface charge of −26 ± 0.15 mV and −24 ± 0.45 mV, respectively. Both BSA-Lac NPs were selectively recognized by ASGPRs as shown by biorecognition, competition, and inhibition assays using an in vitro model of HCC. This justifies pursuing the strategy of using BSA-Lac NPs as potential drug nanovehicles with selective direction toward hepatocellular carcinoma.

Albumin-Albumin/Lactosylated Core-Shell Nanoparticles: Therapy to Treat Hepatocellular Carcinoma for Controlled Delivery of Doxorubicin

“…Previously, LC and HC tBSA/BSALac-Dox NPs were prepared using a desolvation system as previously described. Different concentrations of crosslinker were included to evaluate their impact on encapsulation efficiency [ 24 ]. Control nanoparticles that were synthesized without a BSALac shell were used to compare them with nanoparticles with BSALac shell.…”

“…Therefore, when synthesizing ligand-functionalized nanoparticles, it is crucial to assess specific biorecognition. LC tBSA/BSALac-Dox NPs and HC tBSA/BSALac-Dox NPs have galactose residues in their shell, potentially recognizable by the lectin-type receptors (carbohydrate recognizer) [ 24 ]. In this work, the biorecognition assays were evaluated through the specific recognition of galactose residues by Ricinus communis Agglutinin I (RCA I) and specific cell uptake by HepG2 cells.…”

“…Previously, we reported on the synthesis and characterization of lactosylated (Lac) albumin (BSA) nanoparticles (BSALac NPs), in addition to their specific recognition by the asialoglycoprotein receptor (ASGPR), which is practically exclusively and the most abundant receptor in liver cells [ 24 ]. This information is very important because hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide with an incidence rate similar to that of the mortality rate [ 25 ].…”

<p>Targeted Therapy for Hepatocellular Carcinoma: Co-Delivery of Sorafenib and Curcumin Using Lactosylated pH-Responsive Nanoparticles</p>

“…13 So lactosylated nanoparticle is considered as a good targeted system for HCC treatment. 14 Stimuli-responsive (including reduction, pH, light, and enzyme responsive) nanoparticles were an efficient delivery platform for anticancer drugs, they have many advantages such as improving the availability of drugs and releasing a large number of drugs in response. 15 The extracellular environment of tumors is more acidic than normal tissue, so pH-sensitive nanoparticles are an effective cancer treatment strategy.…”

A Review of Nanotechnology for Targeted Anti-schistosomal Therapy

“…(C) Transmission electron microscopy (TEM) image of Citral-loaded self nano-emulsifying drug delivery system (CIT-SNEDDS). Adapted fromIzham et al (2019) andTeran-Saavedra et al (2019).…”