Polymersome-based targeted delivery of TLR7/8 agonists enhances cancer immunotherapy

]quinolin-4-amine hydrochloride (3M-060), a novel compound with superior immunostimulatory potency encapsulated in nanoscale size polymersomes (ACM-3M-060). ACM-3M-060 elicited stronger induction of pro-inflammatory cytokines than resiquimod (R848) loaded polymersomes (ACM-R848) in human peripheral blood mononuclear cells (PBMCs), while preserving the native activity of the free drug. In a murine CT26 tumor model, intratumoral administration of an ACM-3M-060 analogue labeled with rhodamine led to prolonged retention in the tumor, enhanced drug uptake in the tumor-draining lymph nodes (DLNs) and reduced systemic exposure. Notably, ACM-3M-060 achieved superior tumor growth inhibition compared to the free drug, with a proportion of mice achieving complete tumor regression. Rechallenge with CT26 cells in these animals failed to establish tumors, demonstrating durable antitumor immune memory. This therapeutic effect is primarily driven by TLR7/8-mediated immunomodulation and increased expression of markers of T-cell activity. These findings demonstrate that polymersome delivery enables the safe and effective local administration of potent TLR7/8 agonists such as 3M-060 for cancer immunotherapy.