Abstract
Immune reactions to nanomedicines can be detrimental to the patient and compromise efficacy. However, our recent study characterizing the effects of a type III interferon (IFN-λ) response to lipid nanoparticles complexed with nucleic acids (lipoplexes) suggests that an IFN-λ pretreatment can increase tumor accumulation while decreasing off-target distribution of chemotherapeutic nanomedicines. This project provides a direct follow-up to our previously published works by clarifying 1) which cell type(s) can produce IFN-λ in response to lipoplexes and how the effects of IFN-λ may be propagated in humans. Additionally, we demonstrate 2) that an IFN-λ pretreatment is also capable of altering the accumulation profile of chemotherapeutic small molecules like doxorubicin. Finally, we determined 3) that the subcutaneous administration route for an IFN-λ pretreatment is the most efficacious, and 4) that an IFN-λ pretreatment can significantly increase the survival time of mice receiving Doxil® in a murine CT26 tumor model. With several chemotherapeutic nanomedicines available in the clinic and an IFN-λ product recently completing late phase clinical trials, this study provides the model for a novel anti-cancer treatment regime that can be rapidly translated to the clinic and improve the efficacy of contemporary treatment protocols.