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

Abstract

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.

Microneedle‐assisted transdermal delivery of nanoparticles: Recent insights and prospects

“…Jung et al presented a chemo‐immune therapy for metastatic tumor and melanoma, based on a dissolving MAPs approach fabricated with a PVA/PVP/PEG three‐block co‐polymer matrix. The designed MAPs combining co‐encapsulated nano‐MCs with paclitaxel (PTX), an anticancer drug, and resquimod (R848), an immunomodulator (Jung et al, 2022). This combination can enhance cancer death cell death and promote the tumor antigen activity at the same time.…”

Recent Advances in the Multifunctional Microneedles: From Design to Cancer Preventing, Diagnosis, and Treatment

“…The NMC has the appropriate size to enter tumor-draining lymph nodes (TDLNs) and can synergistically induce immunogenic cell death (ICD) and tumor-associated antigen (TAA) release in melanoma cells (B16F10) at reduced PTX concentrations (Figure 10b). [135]…”

“…b) Schematic diagram of MN-mediated delivery of PTX and R848 to tumor-draining lymph nodes for chemoimmunotherapy of metastatic tumors. Reproduced with permission [135]. Copyright 2022, Wiley-VCH GmbH.…”