Please login first
Antibody-Functionalized Nanoparticles: A Targeted Drug Delivery Strategy
1 , 2 , 1, 3 , 1, 3 , 1, 3 , 4, 5 , 1, 3, 4, 6 , * 2, 3
1  Department of Pharmacy and Food Sciences, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, Spain
2  Department of Physiology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01006, Vitoria-Gasteiz, Spain
3  Microbiology, Infectious Disease, Antimicrobial Agents, and Gene Therapy, IIS Bioaraba, Vitoria-Gasteiz, 01009, Spain
4  Instituto Biofisika (CSIC-UPV/EHU), University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain
5  Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), 48080 Bilbao, Spain
6  Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain
Academic Editor: Arne Skerra

Abstract:

Introduction: Monoclonal antibodies (mAbs) have become pivotal in cancer therapy due to their ability to recognize tumor-associated antigens, triggering immune responses or disrupting signaling pathways essential for tumor growth and survival. Over recent decades, mAbs have been engineered as carriers for cytotoxic agents, enabling targeted delivery, reducing off-target toxicity, and expanding the therapeutic window of chemotherapeutics. Since antitumor efficacy often correlates with drug payload, this study explores a strategy to enhance drug delivery by conjugating a mAb to a drug-loaded nanostructured lipid carrier (NLC) via a maleimide-based reaction.
Methods: NLCs were produced consisting of a disordered solid lipid matrix (comprising blended solid and liquid lipids) and a surfactant-containing aqueous phase, designed to encapsulate poorly soluble drugs. After loading the maleimide lipid containing NLCs with the topoisomerase I inhibitor SN-38, nanoparticles were incubated with Denintuzumab, a CD19 specific antibody, in the presence of a reducing agent. The mixture was next purified through size exclusion chromatography.
Results: The resulting antibody-NLC conjugates are monodisperse (with a PDI of 0.27), exhibit a hydrodynamic diameter of ~140 nm, and retain high target specificity.
Conclusions: It is feasible to conjugate monoclonal antibodies to drug-loaded NLCs. Ongoing work focuses on loading these nanoparticles with the topoisomerase I inhibitor SN-38 and evaluating the targeted delivery efficacy of these nanoparticles in tumor models.

Keywords: Antibody, Nanoparticles, NLC, Drug delivery, Cancer.
Top