Decoration of gold nanoparticles with glycopeptides leads to a lower cellular uptake and liver retention
Unspecific uptake by the liver is one of the main drawbacks of the translation of nanomaterials into clinics, preventing their delivery into diseased tissues. Here, we synthesized gold nanoparticles (GNPs) decorated with a sialic acid-displaying glycopeptide to enhance their specific targeting properties by reducing their uptake inside hepatic cells. We demonstrated the biocompatibility of the glycopeptide-coated GNPs with two different nanomaterial shapes (spherical and rod-like GNPs) and the targeting properties of the glycopeptide were retained in serum-free and protein-rich media. We found that the glycopeptide reduces nanomaterial interaction with hepatic cells by 1.96 times. In the liver, Kupffer cells (KCs) and liver sinusoidal endothelial cells (LSECs) were the only cells that interacted with the GNPs, increasing the expression of sialic acid-binding receptors such as Siglec-1. This work provides potential new strategies to overcome off-target nanomaterial accumulation by manipulating nanomaterial functionalisation with glycans to alter hepatic cell interactions.
Authors
- James S. O’Donnell (ORCID: https://orcid.org/0000-0003-0309-3313)
- Daniel I. R. Spencer (ORCID: https://orcid.org/0000-0001-6386-0890)
- Mahmoud G. Soliman (ORCID: https://orcid.org/0000-0003-4260-0808)
- Alessandro Corbelli (ORCID: https://orcid.org/0000-0001-8545-8050)
- Martina Bruna Violatto (ORCID: https://orcid.org/0000-0002-9016-410X)
- Sergio Enrique Moya (ORCID: https://orcid.org/0000-0002-7174-1960)
- Marco P. Monopoli (ORCID: https://orcid.org/0000-0002-2035-6894)
- Jennifer Fernández Alarcón (ORCID: https://orcid.org/0000-0002-4332-5492)
- Fabio Fiordaliso (ORCID: https://orcid.org/0000-0002-0172-4030)
- Giovanni Sitia (ORCID: https://orcid.org/0000-0003-1024-9128)
- Chiara Cordiglieri (ORCID: https://orcid.org/0000-0002-2013-0043)
- Marko Dobricic
- Tanja Ursula Lüdtke
- Paolo Bigini (ORCID: https://orcid.org/0000-0002-0239-9532)
Institutions
- Royal College of Surgeons in Ireland (IE)
- Vita-Salute San Raffaele University (IT)
- Al-Azhar University (EG)
- Mario Negri Institute for Pharmacological Research (IT)
- CIC biomaGUNE (ES)
- Culham Science Centre (GB)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Ludger (United Kingdom) (GB)
- Istituto Nazionale Genetica Molecolare (IT)
- Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT)
Publication Details
- Journal
- Nanoscale Advances
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d5na00464k
- Citations
- 2
- Primary Topic
- Glycosylation and Glycoproteins Research
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- European Commission
- Science Foundation Ireland
- Associazione Italiana per la Ricerca sul Cancro
- Horizon 2020 Framework Programme
- H2020 Marie Skłodowska-Curie Actions