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Polymer-based nanoparticles loaded with a TLR7 ligand to target the lymph node for immunostimulation

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Widmer Jérôme, Thauvin Cédric, Mottas Inès, Nguyen Van Nga, Delie Florence, Allémann Eric, Bourquin Carole,
Project RLR/TLR combination therapy: Mechanisms of T-cell recruitment into gastric tumors
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Original article (peer-reviewed)

Journal International Journal of Pharmaceutics
Volume (Issue) 535(1-2)
Page(s) 444 - 451
Title of proceedings International Journal of Pharmaceutics
DOI 10.1016/j.ijpharm.2017.11.031

Open Access

Type of Open Access Repository (Green Open Access)


Small-molecule agonists for the Toll-like receptors (TLR) 7 and 8 are effective for the immunotherapy of skin cancer when used as topical agents. Their systemic use has however been largely unsuccessful due to dose-limiting toxicity. We propose a polymer-based nanodelivery system to target resiquimod, a TLR7 ligand, to the lymph node in order to focus the immunostimulatory activity and to prevent a generalized inflammatory response. We demonstrate successful encapsulation of resiquimod in methoxypoly(ethylene glycol)-b-poly(DL-lactic acid) (mPEG-PLA) and mixed poly(DL-lactic-co-glycolic acid) (PLGA)/mPEG-PLA nanoparticles. We show that these particles are taken up mainly by dendritic cells and macrophages, which are the prime initiators of anticancer immune responses. Nanoparticles loaded with resiquimod activate these cells, demonstrating the availability of the immune-stimulating cargo. The unloaded particles are non-inflammatory and do not have cytotoxic activity on immune cells. Following subcutaneous injection in mice, mPEG-PLA and PLGA/mPEG-PLA nanoparticles are detected in dendritic cells and macrophages in the draining lymph nodes, demonstrating the targeting potential of these particles. Thus, polymer-based nanoparticles represent a promising delivery system that allows lymph node targeting for small-molecule TLR7 agonists in the context of systemic cancer immunotherapy.