766
Views
10
CrossRef citations to date
0
Altmetric
Original Research

Monocyte targeting and activation by cationic liposomes formulated with a TLR7 agonist

, , , , , , , , , & show all
Pages 1045-1058 | Published online: 15 Feb 2015
 

Abstract

Objectives: Monocytes are one of the major phagocytic cells that patrol for invading pathogens, and upon activation, differentiate into macrophages or antigen-presenting dendritic cells (DCs) capable of migrating to lymph nodes eliciting an adaptive immune response. The key role in regulating adaptive immune responses has drawn attention to modulate monocyte responses therapeutically within cancer, inflammation and infectious diseases. We present a technology for targeting of monocytes and delivery of a toll-like receptor (TLR) agonist in fresh blood using liposomes with a positively charged surface chemistry.

Methods: Liposomes were extruded at 100 nm, incubated with fresh blood, followed by leukocyte analyses by FACS. Liposomes with and without the TLR7 agonist TMX-202 were incubated with fresh blood, and monocyte activation measured by cytokine secretion by ELISA and CD14 and DC-SIGN expression.

Results: The liposomes target monocytes specifically over lymphocytes and granulocytes in human whole blood, and show association with 75 – 95% of the monocytes after 1 h incubation. Formulations of TMX-202 in cationic liposomes were potent in targeting and activation of monocytes, with strong induction of IL-6 and IL-12p40, and differentiation into CD14+ and DC-SIGN+ DCs.

Conclusion: Our present liposomes selectively target monocytes in fresh blood, enabling delivery of TLR7 agonists to the intracellular TLR7 receptor, with subsequent monocyte activation and boost in secretion of proinflammatory cytokines. We envision this technology as a promising tool in future cancer immunotherapy.

Declaration of interest

The work was funded by the EUREKA Eurostars Programme to the “LIPODEL” project, and from the Danish Ministry of Higher Education and Science under the NABIIT programme. PT Johsnon, M Gad and SS Jensen were former employees at Bioneer. D Zucker, L Parhamifar, JR Henriksen, TL Andresen, H Pourhassan and SS Jensen are employed by DTU. A Barberis and R Maj are employed by Terlomedix. J Henriksen, TL Andresen and SS Jensen are founders of MonTa Biosciences, which are developing cancer immunotherapy based on monocyte targeting technologies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 99.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 876.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.