Microneedle-Directed Drug Delivery to Tumor-Draining Lymph Node for Synergistic Combination Chemoimmunotherapy for Metastatic Cancer

Chemoimmunotherapy based on the combination of anticancer agents and immune modulators is considered as a promising anticancer therapeutic approach that leads to tumor cell death and tumor-specific immune responses, suppressing the growth of metastatic tumors in distal sites. However, the undesirable systemic immune responses and cytotoxicity caused by chemoimmunotherapy should be reduced prior to clinical translation. This study aimed to design an amphiphilic triblock copolymer-based dissolving microneedle (MN), which can generate nanomicelles (PTX/R848@NMC) containing a poorly water-soluble anticancer drug, paclitaxel (PTX), and an immune modulator, resiquimod (R848). The combination of PTX and R848 synergistically induces immunogenic cell death (ICD) in melanoma cells (B16F10) at reduced PTX concentrations without compromising the viability and functions of dendritic cells (DCs). After cutaneous application of MN to tumor-bearing mice, the PTX/R848@NMC generated from the dissolution of MN can migrate to tumor-draining lymph nodes, resulting in the death of metastatic tumor cells and the activation and maturation of DCs. Tumor-specific immune responses can effectively suppress the growth of primary and metastatic secondary tumors.