Glycosylation-driven interactions of nanoparticles with the extracellular matrix: Implications for inflammation and drug delivery
Artikel i vetenskaplig tidskrift, 2025

Cationic nanoparticles (NPs) are emerging as promising carriers for intra-articular drug delivery, particularly for osteoarthritis (OA) where treatment options are limited. However, the clinical translation is challenged by an incomplete understanding of NP interactions within pathological environments. While the influence of the protein coronas on NP behavior has been extensively studied, the specific role of glycoproteins in the extracellular matrix (ECM) remains underexplored, representing a significant knowledge gap. This study investigates how glycosylation-driven interactions between polymeric NPs and enzyme-degraded cartilage biomolecules such as glycosaminoglycans (GAGs) affect NP-ECM aggregate formation and subsequent inflammatory responses. Using an ex vivo model of cartilage degradation induced by catabolic enzymes– hyaluronidase, ADAMTS5 and collagenase– a novel model system was developed to specifically study the behavior of small (<10 nm) and large (∼270 nm) cationic NPs in glycoprotein-enriched environments. Atomic force microscopy and dynamic light scattering revealed distinct mesh-like structures formed by the NP aggregates following different enzymatic treatments, confirming the adsorption of glycosylated fragments onto the particles. While total protein content showed minimal differences between NP samples, smaller NPs demonstrated a prominent association with GAGs such as hyaluronic acid and aggrecan, as demonstrated by circular dichroism. These ECM-NP interactions significantly influenced the immunological response, as evidenced by differential cytokine production from macrophages exposed to the aggregates. Our findings underscore the crucial, yet underappreciated, role of glycoproteins in determining NP behavior in pathological environments. Accounting for glycoprotein interactions into the design of nanomaterial and drug delivery systems could significantly improve therapeutic outcomes by enhanced targeting precision, optimized delivery, and effectively modulating immune responses in OA and other complex diseases.

Biomolecular corona

Nanoparticles

Extracellular matrix

Immunomodulation

Polymeric

Glycosylation

Protein corona

Författare

Ula von Mentzer

Chalmers, Life sciences, Kemisk biologi

Fritjof Havemeister

Chalmers, Life sciences, Kemisk biologi

Loise Råberg

Chalmers, Life sciences, Kemisk biologi

Hemapriya Kothuru Chinnadurai

Chalmers, Life sciences, Kemisk biologi

Gizem Erensoy

Chalmers, Life sciences, Kemisk biologi

Elin Esbjörner Winters

Chalmers, Life sciences, Kemisk biologi

Alexandra Stubelius

Chalmers, Life sciences, Kemisk biologi

Biomaterials Advances

2772-9508 (eISSN)

Vol. 171 214230

Sialinsyrainhibering med unik behandlingsstrategi för artros

Harald och Greta Jeanssons Stiftelse (JeanssonsStift.beslut2021), 2022-01-01 -- 2024-09-30.

Vetenskapsrådet (VR) (2021-01870), 2021-01-01 -- 2021-12-31.

Hur påverkar sockerstrukturer i brosket inflammationen vid artros?

Reumatikerförbundet (R-981253), 2023-04-01 -- 2024-12-31.

Jämställdhet för excellens (Genie)

Stiftelsen Chalmers tekniska högskola, 2019-01-01 -- 2028-12-31.

Sialic Acid-Mediated Pathogenic Mechanisms in Osteoarthritis

Konung Gustaf V:s 80-årsfond (FAI-2022-0872), 2023-06-01 -- 2024-12-31.

Precision Medicine for Rheumatoid Arhtritis: Utilizing Disease Mechanisms to Achieve Self-Adjusting Nanotherapeutics

Stiftelsen Anna-Greta och Holger Crafoords fond (CR2021-0024), 2021-10-01 -- 2023-08-15.

Ämneskategorier (SSIF 2025)

Molekylärbiologi

Biomaterialvetenskap

DOI

10.1016/j.bioadv.2025.214230

PubMed

39983501

Mer information

Senast uppdaterat

2025-03-21