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

Abstract

Doxorubicin (Dox) is the most widely used chemotherapeutic agent and is considered a highly powerful and broad-spectrum for cancer treatment. However, its application is compromised by the cumulative side effect of dose-dependent cardiotoxicity. Because of this, targeted drug delivery systems (DDS) are currently being explored in an attempt to reduce Dox systemic side-effects. In this study, DDS targeting hepatocellular carcinoma (HCC) has been designed, specifically to the asialoglycoprotein receptor (ASGPR). Dox-loaded albumin-albumin/lactosylated (core-shell) nanoparticles (tBSA/BSALac NPs) with low (LC) and high (HC) crosslink using glutaraldehyde were synthesized. Nanoparticles presented spherical shapes with a size distribution of 257 ± 14 nm and 254 ± 14 nm, as well as an estimated surface charge of −28.0 ± 0.1 mV and −26.0 ± 0.2 mV, respectively. The encapsulation efficiency of Dox for the two types of nanoparticles was higher than 80%. The in vitro drug release results showed a sustained and controlled release profile. Additionally, the nanoparticles were revealed to be biocompatible with red blood cells (RBCs) and human liver cancer cells (HepG2 cells). In cytotoxicity assays, Dox-loaded nanoparticles decrease cell viability more efficiently than free Dox. Specific biorecognition assays confirmed the interaction between nanoparticles and HepG2 cells, especially with ASGPRs. Both types of nanoparticles may be possible DDS specifically targeting HCC, thus reducing side effects, mainly cardiotoxicity. Therefore, improving the quality of life from patients during chemotherapy.

Efficacy and safety of raltitrexed‐based transcatheter arterial chemoembolization for intermediate and advanced hepatocellular carcinoma: A multicenter real‐world study

“…The AEs of epirubicin and adriamycin are mainly cardiotoxicity. 24,25 5-Fluorouracil requires continuous intravenous infusion, and AEs such as leukopenia are common. 26 The most common AE of cisplatin is gastrointestinal reaction, and repeated use aggravates nephrotoxicity.…”

Hypoxia-Activated Albumin-Binding Exatecan Prodrug for Cancer Therapy

“…It also has the potential to extend the half-life of the drug . Nowadays, drug delivery systems that use albumin as a drug carrier include drug conjugates, drug adducts, albumin-binding derivatives, and nanoparticles. − Among them, albumin-binding derivatives especially the albumin-binding prodrugs receive much attention. , Albumin-binding prodrugs are designed with the concept of rapid and selective covalent binding to the cysteine 34 position (Cys-34) of serum albumin after intravenous administration to form a macromolecular drug delivery system . Since covalent binding of a prodrug to albumin greatly reduces the antitumor activity, most of the current research is focused on stimulus-responsive albumin-binding prodrugs. , A stimulus-responsive albumin-binding delivery system can effectively accumulate at the tumor site, respond to internal or external stimuli, and release drugs.…”

Preliminary outcomes of DEB-TACE loaded with raltitrexed in the treatment of unresectable or recurrent hepatocellular carcinoma

“…As one of the most widely used chemotherapeutic agents, doxorubicin is considered a broad-spectrum, highly powerful for HCC treatment. Unfortunately, its application is compromised by dose-dependent cardiotoxicity [ 26 ]. Doxorubicin-loaded nanoparticles may be used as a possible drug delivery system for reducing this side effects [ 26 ].…”