Pairing Nanoparticles Geometry with TLR Agonists to Modulate Immune Responses for Vaccine Development.

Autor:	Bhoge PR; Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India., Mardhekar S; Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India., Toraskar S; Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India., Subramani B; Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India., Kikkeri R; Indian Institute of Science Education and Research, Dr. Homi Bhabha Road, Pashan, Pune, Maharashtra 411008, India.
Jazyk:	angličtina
Zdroj:	ACS applied bio materials [ACS Appl Bio Mater] 2022 Dec 19; Vol. 5 (12), pp. 5675-5681. Date of Electronic Publication: 2022 Nov 14.
DOI:	10.1021/acsabm.2c00716
Abstrakt:	Nanotechnology-based vaccine development necessitates understanding the crucial biophysical properties of nanostructures that alter immune responses. In this study, we demonstrate the synergistic effect of gold nanoparticles (AuNPs) shapes with toll-like receptor (TLR) agonists in immune modulation activity. Our results showed that CpG- and imidazoquinoline-conjugated rod-shaped AuNPs display relatively fast uptake by bone marrow-derived macrophage cells but exhibit poor immunogenic responses compared to their spherical and star-shaped AuNP counterparts. Surprisingly, star-shaped AuNPs exhibited intense pro-inflammatory cytokine secretion. Further mechanistic studies showed that star-shaped AuNPs were abundantly localized in the late endosome and lysosomal regions, whereas rod-shaped AuNPs were majorly sequestered in the mitochondrial region. These findings reveal that the shape of the nanostructures plays a pivotal role in driving the adjuvant molecules toward their receptors and altering immune responses.
Databáze:	MEDLINE
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