Enhancing precision medicine : Bispecific antibody-mediated targeted delivery of lipid nanoparticles for potential cancer therapy

Copyright © 2024 Elsevier B.V. All rights reserved..

The precise delivery of therapeutic agents to specific cell populations, including cancer cells, remains a target in modern medicine, to enhance treatment efficacy, while minimizing unintended side effects. This study presents a strategy utilizing bispecific antibodies for the targeted delivery of nucleic acid drugs to the surface of glucose-regulated protein 78 (GRP78)-overexpressing cancer cells. Strong binding affinity of the bispecific antibodies to GRP78-overexpressing cancer cells, including HEPG2 cells, confirmed the tumor-targeting potential of this platform. Functional analyses demonstrated the role of the bispecific antibodies in enhancing lipid nanoparticle (LNP) uptake, causing increased gene expression levels of nucleic acid drugs loaded within LNPs. In vivo imaging confirmed the potency of the bispecific-antibody-modified LNPs in delivering nucleic acid drugs to tumors and sustaining therapeutic expression levels. In vivo therapy results indicated that the bispecific antibodies improved the antitumor activity of PE38-loaded LNPs in tumors overexpressing surface GRP78. This study pioneered a bispecific-antibody-centered platform for the targeted delivery of nucleic acid drugs. The robust antigen-antibody binding affinity, tumor-selective interactions, enhanced cellular uptake, and proficient gene expression promise to advance precision therapeutics in oncology. Continued refinement and translation of this drug delivery strategy are important to unlock its full clinical potential.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:654

Enthalten in:

International journal of pharmaceutics - 654(2024) vom: 10. Apr., Seite 123990

Sprache:

Englisch

Beteiligte Personen:

Zhang, Yue [VerfasserIn]
Gu, Xiaoyan [VerfasserIn]
Huang, Lili [VerfasserIn]
Yang, Yani [VerfasserIn]
He, Jun [VerfasserIn]

Links:

Volltext

Themen:

Antibodies, Bispecific
Bispecific antibody
Endoplasmic Reticulum Chaperone BiP
GRP78 protein
Journal Article
Lipid Nanoparticles
Lipid nanoparticles
Liposomes
Nucleic Acids
Tumor cells
Tumor target

Anmerkungen:

Date Completed 09.04.2024

Date Revised 09.04.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ijpharm.2024.123990

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369569350