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Research Article | Open Access

Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights

Ana M. López-Estévez1,2,3Y. Zhang4María Medel5Iker Arriaga6Lucía Sanjurjo3Cristian Huck-Iriart7Nicola G. A. Abrescia6,8María J. Vicent5Defang Ouyang4Dolores Torres2María José Alonso1,2,3( )
Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), University of Santiago de Compostela, Santiago de Compostela 15782, Spain
Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, Santiago de Compostela 15782, Spain
Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela 15782, Spain
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS), University of Macau, Macau 999078, China
Polymer Therapeutics Laboratory and CIBERONC Prince Felipe Research Centre, Valencia E-46012, Spain
Structure and Cell Biology of Viruses Lab, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio 48160, Spain
ALBA Synchrotron Light Source, Experiments Division, Cerdanyola del Vallès, Barcelona 08290, Spain
IKERBASQUE, Basque Foundation for Science, Bilbao 48009, Spain
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Graphical Abstract

Here we report a novel and versatile nanoplatform for the delivery of clinical doses of monoclonal antibodies alongside a comprehensive characterization of their organization and biological behavior.

Abstract

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies (mAbs). Despite their increasing potential, mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular targets. Nanotechnology offers promising solutions to overcome this limitation, however, formulation challenges remain. These challenges are the limited loading capacity (often insufficient to achieve clinical dosing), the complex formulation methods, and the insufficient characterization of mAb-loaded nanocarriers. Here, we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies (HANAs) specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity (50%, w/w). HANAs composed by an mAb, modified HA and phosphatidylcholine (PC) resulted in sizes of ~ 100 nm and neutral surface charge. Computational modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and PC. HANAs composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy (cryo-TEM), asymmetrical flow field-flow fractionation (AF4), and small-angle X-ray scattering (SAXS). These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic HA. In vitro experiments in cancer cell lines and macrophages confirmed HANAs’ low toxicity and ability to transport mAbs to the intracellular space. The reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was assessed. In conclusion, these results underscore the suitability of HANAs technology to load and deliver biologicals, which holds promise for future clinical translation.

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Nano Research
Pages 9111-9125
Cite this article:
López-Estévez AM, Zhang Y, Medel M, et al. Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery – design, characterization, and biological insights. Nano Research, 2024, 17(10): 9111-9125. https://doi.org/10.1007/s12274-024-6826-8
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Received: 31 January 2024
Revised: 03 June 2024
Accepted: 13 June 2024
Published: 11 July 2024
© The Author(s) 2024

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