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

Article Article scientifique Article Polymer-based nanoparticles loaded with a TLR7 ligand to target the lymph node for immunostimulation eng 2018 author Widmer Jérôme author Thauvin Cédric 808885 author Mottas Inès 860089 author Nguyen Van Nga 804267 author Delie Salmon Florence 121330 author Allémann Eric 0000-0002-6598-9521 26730 author Bourquin Carole 0000-0003-3862-4583 854541 444-451 10.1016/j.ijpharm.2017.11.031 29157965 0378-5173 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. Nanoparticl Immunostimulation Resiquimod TLR7 Dewey 615 31 Section des sciences pharmaceutiques 17 false 1278 Immunopharmacologie du cancer 883 Technologie pharmaceutique International Journal of Pharmaceutics 535 1-2 c8fac5de-dc82-400b-b5be-ed2e58f26cc9 Article (Accepted version) Public ManuscritWidmerRevised.pdf 380456 application/pdf openAccess Faculté des sciences / Section des sciences pharmaceutiques

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Polymer-based nanoparticles loaded with a TLR7 ligand to target the lymph node for immunostimulation	International Journal of Pharmaceutics			2018	638	627

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Nguyen, Van Nga