Effect of Several HIV Antigens Simultaneously Loaded with G2-NN16 Carbosilane Dendrimer in the Cell Uptake and Functionality of Human Dendritic Cells

Bioconjug Chem. 2016 Dec 21;27(12):2844-2849. doi: 10.1021/acs.bioconjchem.6b00623. Epub 2016 Dec 1.

Abstract

Dendrimers are highly branched, star-shaped, and nanosized polymers that have been proposed as new carriers for specific HIV-1 peptides. Dendritic cells (DCs) are the most-potent antigen-presenting cells that play a major role in the development of cell-mediated immunotherapy due to the generation and regulation of adaptive immune responses against HIV-1. This article reports on the associated behavior of two or three HIV-derived peptides simultaneously (p24/gp160 or p24/gp160/NEF) with cationic carbosilane dendrimer G2-NN16. We have found that (i) immature DCs (iDCs) and mature (mDCs) did not capture efficiently HIV peptides regarding the uptake level when cells were treated with G2-NN16-peptide complex alone; (ii) the ability of DCs to migrate was not depending on the peptides presence; and (iii) with the use of molecular dynamic simulation, a mixture of peptides decreased the cell uptake of the other peptides (in particular, NEF hinders the binding of more peptides and is especially obstructing of the binding of gp160 to G2-NN16). The results suggest that G2-NN16 cannot be considered as an alternative carrier for delivering two or more HIV-derived peptides to DCs.

MeSH terms

  • Dendrimers / chemistry*
  • Dendrimers / pharmacokinetics
  • Dendritic Cells / drug effects*
  • HIV Antigens / chemistry*
  • HIV Antigens / pharmacology
  • HIV Core Protein p24 / chemistry
  • HIV Envelope Protein gp160 / chemistry
  • Humans
  • Molecular Dynamics Simulation
  • Silanes / chemistry*
  • Silanes / pharmacokinetics
  • Static Electricity

Substances

  • 2G-NN16
  • Dendrimers
  • HIV Antigens
  • HIV Core Protein p24
  • HIV Envelope Protein gp160
  • Silanes
  • carbosilane