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

Widmer, Jérôme; Thauvin, Cédric; Mottas, Inès; Nguyen, Van; Delié, Florence; Allémann, Éric; Bourquin, Carole

doi:10.1016/j.ijpharm.2017.11.031

Cited by 51 publications

(29 citation statements)

References 32 publications

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“…26 We have previously shown for other types of fluorescently labelled nanoparticles that the uptake in this macrophage cell line mirrors the uptake seen in primary murine antigen-presenting cells. 55,56 The uptake of non-fluorescent NCs by macrophages was proven by TEM, SEM and elemental mapping experiments, showing hollow particles made of TiO 2 inside the cells. Comparing EDS spectra, intracellular silver concentrations were found to be higher in the intracellular nanocapsules than in NC-free areas of the cell.…”

Section: Discussionmentioning

confidence: 97%

<p>Silver-Containing Titanium Dioxide Nanocapsules for Combating Multidrug-Resistant Bacteria</p>

Hérault

Wagner

Abram

et al. 2020

IJN

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Background: Joint arthroplasty has improved the quality of life of patients worldwide, but infections of the prosthesis are frequent and cause significant morbidity. Antimicrobial coatings for implants promise to prevent these infections. Methods: We have synthesized nanocapsules of titanium dioxide in amorphous or anatase form containing silver as antibacterial agent and tested their impact on bacterial growth. Furthermore, we explored the possible effect of the nanocapsules on the immune system. First, we studied their uptake into macrophages using a combination of electron microscopy and energy-dispersive spectroscopy. Second, we exposed immune cells to the nanocapsules and checked their activation state by flow cytometry and enzyme-linked immunosorbent assay. Results: Silver-containing titanium dioxide nanocapsules show strong antimicrobial activity against both E. coli and S. aureus and even against a multidrug-resistant strain of S. aureus. We could demonstrate the presence of the nanocapsules in macrophages, but, importantly, the nanocapsules did not affect cell viability and did not activate proinflammatory responses at doses up to 20 μg/mL. Conclusion: Our bactericidal silver-containing titanium dioxide nanocapsules fulfill important prerequisites for biomedical use and represent a promising material for the coating of artificial implants.

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Section: Discussionmentioning

confidence: 97%

<p>Silver-Containing Titanium Dioxide Nanocapsules for Combating Multidrug-Resistant Bacteria</p>

Hérault

Wagner

Abram

et al. 2020

IJN

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“…A local immune reaction was observed in the lymph nodes draining the injection sites. In fact, one goal of drug delivery systems is to target the immune-activating drugs to the site of induction of an immune response, such as the tumor-draining lymph nodes 49 . In addition, due to their phagocytic nature, dendritic cells can be selectively targeted by particulate delivery systems.…”

Section: Novel Drug Delivery Systems For Tlr and Rlr Agonistsmentioning

confidence: 99%

“…Thus, TLR and RLR agonists can be delivered directly to dendritic cells by nanoparticles prepared from inorganic materials such as gold 50 or silica 51,52 , or by biodegradable particles from e.g. gelatin [53][54][55] , spider silk 56 or polymers 49,57 . The use of RNAlipoplexes, where the RNA functions as a TLR7 agonist, has led to systemic targeting of dendritic cells, induction of IFN-I and potent induction of tumor-specific T cells in patients 58 .…”

Section: Novel Drug Delivery Systems For Tlr and Rlr Agonistsmentioning

confidence: 99%

Harnessing the immune system to fight cancer with Toll-like receptor and RIG-I-like receptor agonists

Bourquin

Pommier

Hotz

2020

Pharmacological Research

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Cancer immunotherapy has come of age with the advent of immune checkpoint inhibitors. In this article we review how agonists for receptors of the innate immune system, the Toll-like receptors and the RIG-I-like receptors, impact anticancer immune responses. Treatment with these agonists enhances the activity of anticancer effector cells, such as cytotoxic T cells and NK cells, and at the same time blocks the activity of immunosuppressive cell types such as regulatory T cells and myeloid-derived suppressor cells. These compounds also impact the recruitment of immune cells to the tumor. The phenomena of pattern-recognition receptor tolerance and reprogramming and their implications for immunotherapy are discussed. Finally, novel delivery systems that target the immune-stimulating drugs to the tumor or the tumordraining lymph nodes to enhance their efficacy and safety are presented.

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“…[36] This is in contrast to a previous publication by the authors where polymer-based nanoparticles were used to deliver R848 to the lymph nodes. [37] The larger size of those particles (> 150 nm)…”

Section: Lymph Node Accumulation and In Vivo Immune Activation By Ampmentioning

confidence: 99%

Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation

et al. 2019

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Although immunotherapy shows great promise for the long-term control of cancer, many tumors still fail to respond to treatment. To improve the outcome, the delivery of immunostimulants to the lymph nodes draining the tumor, where the antitumor immune response is initiated, is key. Efforts to use nanoparticles as carriers for cancer immunotherapy have generally required targeting agents and chemical modification of the drug, and have unfortunately resulted in low delivery and therapeutic efficiency. Here, we report on the efficacy of gold nanoparticles with approximately 5 nm hydrodynamic diameter coated with a mixture of 1-octanethiol and 11-mercaptoundecanesulfonic acid for the delivery of an immunostimulatory TLR7 ligand to tumor-draining lymph nodes. The drug was loaded without modification through nonspecific adsorption into the ligand shell of the nanoparticles, taking advantage of their amphiphilic nature. After loading, nanoparticles retained their stability in solution without significant premature release of the drug, and the drug cargo was immunologically active. Upon subcutaneous injection into tumor-bearing mice, the drug-loaded particles were rapidly transported to the tumor-draining lymph nodes. There, they induced a local immune activation and fostered a cytotoxic T-cell response that was specific for the tumor. Importantly, the particle-delivered TLR7 ligand blocked the growth of large established tumors and significantly prolonged survival compared to the free form of the drug. Thus, we demonstrate for the first time that nanoparticle delivery of a TLR7 immunostimulant to the tumor-draining lymph nodes enhances antitumor immunity and improves the outcome of cancer immunotherapy.

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

Cited by 51 publications

References 32 publications

<p>Silver-Containing Titanium Dioxide Nanocapsules for Combating Multidrug-Resistant Bacteria</p>

<p>Silver-Containing Titanium Dioxide Nanocapsules for Combating Multidrug-Resistant Bacteria</p>

Harnessing the immune system to fight cancer with Toll-like receptor and RIG-I-like receptor agonists

Amphiphilic nanoparticle delivery enhances the anticancer efficacy of a TLR7 ligand via local immune activation

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