Albumin-Albumin/Lactosylated Core-Shell Nanoparticles: Therapy to Treat Hepatocellular Carcinoma for Controlled Delivery of Doxorubicin |
| |
Authors: | Nayelli Guadalupe Teran-Saavedra Jose Andrei Sarabia-Sainz Enrique Fernando Velzquez-Contreras Gabriela Ramos-Clamont Montfort Martín Pedroza-Montero Luz Vazquez-Moreno |
| |
Institution: | 1.Departamento de Investigacion en Polimeros y Materiales, Universidad de Sonora, Bulevar Luis Encinas y Rosales s/n, Colonia Centro, Hernosillo, Sonora 83000, Mexico; (N.G.T.-S.); (E.F.V.-C.);2.Departamento de Investigacion en Física, Universidad de Sonora, P.O. Box 5-088, Hermosillo, Sonora 83190, Mexico; ;3.Centro de Investigacion en Alimentacion y Desarrollo, A.C. Carretera Gustavo E. Aztiazaran 46, Hermosillo, Sonora 83304, Mexico; (G.R.-C.M.); (L.V.-M.) |
| |
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. |
| |
Keywords: | doxorubicin drug delivery systems hepatocellular carcinoma asialoglycoprotein receptor lactosylated albumin core-shell nanoparticles |
|
|