Dipalmitoyl-phosphatidylserine-filled cationic maltodextrin nanoparticles exhibit enhanced efficacy for cell entry and intracellular protein delivery in phagocytic THP-1 cells

Abstract Vaccination through the upper respiratory tract is a promising strategy, and particulate antigens, such as antigens associated with nanoparticles, triggered a stronger immune response than the sole antigens. Cationic maltodextrin-based nanoparticles loaded with phosphatidylglycerol (NPPG) are efficient for intranasal vaccination but non-specific to trigger immune cells. Here we focused on phosphatidylserine (PS) receptors, specifically expressed by immune cells including macrophages, to improve nanoparticle targeting through an efferocytosis-like mechanism. Consequently, the lipids associated with NPPG have been substituted by PS to generate cationic maltodextrin-based nanoparticles with dipalmitoyl-phosphatidylserine (NPPS). Both NPPS and NPPG exhibited similar physical characteristics and intracellular distribution in THP-1 macrophages. NPPS cell entry was faster and higher (two times more) than NPPG. Surprisingly, competition of PS receptors with phospho-L-serine did not alter NPPS cell entry and annexin V did not preferentially interact with NPPS. Although the protein association is similar, NPPS delivered more proteins than NPPG in cells. On the contrary, the proportion of mobile nanoparticles (50%), the movement speed of nanoparticles (3 µm/5 min), and protein degradation kinetics in THP-1 were not affected by lipid substitution. Together, the results indicate that NPPS enter cells and deliver protein better than NPPG, suggesting that modification of the lipids of cationic maltodextrin-based nanoparticles may be a useful strategy to enhance nanoparticle efficacy for mucosal vaccination..

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:14

Enthalten in:

Biomolecular concepts - 14(2023), 1 vom: 28. Juni

Sprache:

Englisch

Beteiligte Personen:

Brinkhuizen, Clément [VerfasserIn]
Shapman, Damien [VerfasserIn]
Lebon, Alexis [VerfasserIn]
Bénard, Magalie [VerfasserIn]
Tardivel, Meryem [VerfasserIn]
Dubuquoy, Laurent [VerfasserIn]
Galas, Ludovic [VerfasserIn]
Carpentier, Rodolphe [VerfasserIn]

Links:

Volltext [kostenfrei]

BKL:

42.13 / Molekularbiologie

Anmerkungen:

© 2023 the author(s), published by De Gruyter

doi:

10.1515/bmc-2022-0029

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

GRUY00899840X