Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Volume 181, Issue -, Pages 398-409Publisher
ELSEVIER
DOI: 10.1016/j.ijbiomac.2021.03.148
Keywords
Carboxymethyl chitosan; DCS cells; Hydroxypropyltrimethyl ammonium chloride; chitosan; Immunostimulatory activities; Nanoparticles
Funding
- National Key Research and Development Program of China [2018YFC0311300]
- Key Research and Development Program of Shandong Province [2019GHY112015, 2019YYSP028]
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This study generated chitosan nanoparticles and examined their effects on dendritic cells, finding that 200kDa NO-CMC-HACC nanoparticles showed strong potential as immunological adjuvants.
In this study, we generated chitosan nanoparticles by exploiting the electrostatic interactions between positively charged hydroxypropyltrimethyl ammonium chloride chitosan (HACC) and negatively charged carboxymethyl chitosan (CMC), and examined the effects of altering the molecular weight and carboxymethyl substitution sites of the chitosan molecules. Particle size, potential, and encapsulation efficiency of the various chitosan nano particles were examined; the particle size range was 162.40-332.80 nm, the charge range was 19.50-40.60 mV, and the encapsulation efficiency range was 48.4-70.7%. We then examined the immunostimulatory effects of the nanoparticle variants on dendritic cells (DCs); we found that the site of carboxymethyl substitution significantly affected the immunostimulatory effects of the nanoparticles. Two nanoparticle types, 200 kDa N,O-carboxymethyl chitosan-HACC (NO-CMC-HACC) and N-carboxymethyl chitosan-HACC (N-CMC-HACC), greatly promoted the expression of interleukin-6, tumor necrosis factor, and interleukin-1 beta in DCs. Moreover, NO-CMC-HACC nanoparticles caused an increase in major histocompatibility complex-II (MHC-II), CD11c, CD80, and CD86 secretion in DCs, indicating that these nanoparticles promoted antigen presentation. We then examined chitosan nanoparticle uptake by DCs using laser confocal microscopy; we found that the NO-CMC-HACC nanoparticles were more readily absorbed by DCs compared to the N-CMC-HACC nanoparticles. Therefore, we concluded that 200 kDa NO-CMCHACC nanoparticles exhibited strong potential as immunological adjuvants. (c) 2021 Elsevier B.V. All rights reserved.
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