Skip to Main content Skip to Navigation
Journal articles

Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy

Abstract :

Tumor-induced expansion of myeloid-derived suppressor cells (MDSCs) is known to impair the efficacy of cancer immunotherapy. Among pharmacological approaches for MDSC modulation, chemotherapy with selected drugs has a considerable interest due to the possibility of a rapid translation to the clinic. However, such approach is poorly selective and may be associated with dose-dependent toxicities. In the present study, we showed that lipid nanocapsules (LNCs) loaded with a lauroyl-modified form of gemcitabine (GemC12) efficiently target the monocytic MDSC subset. Subcutaneous administration of GemC12-loaded LNCs reduced the percentage of spleen and tumor-infiltrating M-MDSCs in lymphoma and melanoma-bearing mice, with enhanced efficacy when compared to free gemcitabine. Consistently, fluorochrome-labeled LNCs were preferentially uptaken by monocytic cells rather than by other immune cells, in both tumor-bearing mice and human blood samples from healthy donors and melanoma patients. Very low dose administration of GemC12-loaded LNCs attenuated tumor-associated immunosuppression and increased the efficacy of adoptive T cell therapy. Overall, our results show that GemC12-LNCs have monocyte-targeting properties that can be useful for immunomodulatory purposes, and unveil new possibilities for the exploitation of nanoparticulate drug formulations in cancer immunotherapy.

Document type :
Journal articles
Complete list of metadatas

https://hal.archives-ouvertes.fr/hal-01392469
Contributor : Okina Université d'Angers <>
Submitted on : Friday, November 4, 2016 - 1:54:59 PM
Last modification on : Sunday, May 24, 2020 - 2:18:04 AM

Identifiers

Collections

Citation

Maria Sasso, Giovanna Lollo, Marion Pitorre, Samantha Solito, Laura Pinton, et al.. Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy. Biomaterials, Elsevier, 2016, 96, pp.47-62. ⟨10.1016/j.biomaterials.2016.04.010⟩. ⟨hal-01392469⟩

Share

Metrics

Record views

447