Polyinosinic/Polycytidylic Lipid Nanoparticles Enhance Immune Cell Infiltration and Improve Survival in the Glioblastoma Mouse Model.

ABSTRACT: Glioblastoma (GBM) immunotherapy is particularly challenging due to the pro-tumorigenic microenvironment, marked by low levels and inactive immune cells. Toll-like receptor (TLR) agonists have emerged as potent immune adjuvants but failed to show improved outcomes in clinical trials when administered as a monotherapy. We hypothesize that a combined nanoparticulate formulation of TLR agonist and immunogenic cell death-inducing drug (doxorubicin) will synergize to induce improved GBM immunotherapy. Lipid nanoparticle (LNP) formulations of the TLR agonists CpG and polyinosinic/polycytidylic (pIpC), with and without Dox, were first prepared, achieving an encapsulation efficiency >75% and a size <140 nm. In vitro studies identified that LNP pIpC was superior to CpG at activating bone marrow-der

SUBMITTER: Brußeler MMT 

PROVIDER: S-EPMC11615939 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature