Biology subjects

Charbonniere, L.

Publications and source records attributed to Charbonniere, L..

2 recordsLinked to original sources

bioRxiv2024

Nanomaterials trigger functional responses in primary human immune cells

Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials on the immune system remains unknown. Here, we characterize the molecular and functional response of human NK cells and pan T cells to a selection of five NPs that are commonly used in biomedical applications. After a pre-screen to evaluate the toxicity of these nanomaterials on immune cells, we selected ultrasmall silica-based gadolinium (Si-Gd) NPs and poly(lactic-co-glycolic acid) (PLGA) NPs for further investigation. Bulk RNA-sequencing and flow cytometry analysis showcase that PLGA NPs trigger a transcriptional priming towards activation in NK and pan T cells. While PLGA NPs improved NK cells anti-tumoral functions in cytokines-deprived environment, Si-Gd NPs significantly impaired T cells activation as well as functional responses to a polyclonal antigenic stimulation. Altogether, we identified PLGAs NPs as suitable and promising candidates for further targeting approaches aiming to reactivate the immune system of cancer patients.

immunology↗

bioRxiv2024

Reinforced polymer-nanoparticle hydrogels for subcutaneous and sustained delivery of trastuzumab

In oncology, the advent of monoclonal antibody (mAbs) therapeutics represents a major breakthrough in various cancer diseases. However, these biotherapies often necessitate iterative hospital visits for intravenous infusion that can alter patients quality of life and contribute to the chronic saturation of hospitals. Interestingly, subcutaneous formulations of various mAbs offer a promising alternative facilitating faster administration compared with traditional intravenous methods, while still maintaining the same dosing schedule and providing time-saving advantages. Here, we developed an injectable mAb delivery platform using -cyclodextrin (CD)-reinforced polymer-nanoparticle hydrogels to perform a subcutaneous injection but also to delay the release of mAbs. By leveraging the versatility of our platform, we formulated hyaluronic acid- and alginate-based injectable drug depots by simply mixing components that are generally regarded as safe (GRAS). We used trastuzumab for the polymer-antibody complexation. The hydrogel depots delayed mAb release up to at least 3 days in both in vitro and in vivo mice models, outperforming clinically approved Herceptin subcutaneous formulation composed of trastuzumab with recombinant human hyaluronidase (rHuPH20).

bioengineering↗