Hybrid LNP Prime Dendritic Cells for Nucleotide Delivery.
Riddha DasElias A HalabiIna R FredrichJuhyun OhHannah M PetersonXinying GeElla ScottRainer H KohlerChristopher S GarrisRalph WeisslederPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
The efficient activation of professional antigen-presenting cells-such as dendritic cells (DC)-in tumors and lymph nodes is critical for the design of next-generation cancer vaccines and may be able to provide anti-tumor effects by itself through immune stimulation. The challenge is to stimulate these cells without causing excessive toxicity. It is hypothesized that a multi-pronged combinatorial approach to DC stimulation would allow dose reductions of innate immune receptor-stimulating TLR3 agonists while enhancing drug efficacy. Here, a hybrid lipid nanoparticle (LNP) platform is developed and tested for double-stranded RNA (polyinosinic:polycytidylic acid for TLR3 agonism) and immune modulator (L-CANDI) delivery. This study shows that the ≈120 nm hybrid nanoparticles-in-nanoparticles effectively eradicate tumors by themselves and generate long-lasting, durable anti-tumor immunity in mouse models.
Keyphrases
- dendritic cells
- immune response
- induced apoptosis
- lymph node
- regulatory t cells
- cell cycle arrest
- innate immune
- inflammatory response
- toll like receptor
- oxidative stress
- papillary thyroid
- endoplasmic reticulum stress
- emergency department
- young adults
- early stage
- cell proliferation
- weight loss
- high throughput
- nucleic acid
- pi k akt
- adverse drug
- light emitting
- childhood cancer