Amplifying the Immune Activity of Metal Ions through Metal–Phenolic Complexation
Zhaoran Wang, Jingqu Chen, Tianzheng Wang, Robert De Rose, Christina Cortez‐Jugo, Frank Caruso
Abstract
The immune-modulatory properties of metal ions have contributed to vaccination and immunotherapy (i.e., metalloimmunotherapy) for the prevention and treatment of various diseases. Developing an enabling approach that can readily incorporate metal ions in vaccine formulations and deliver them with controllable pharmacokinetics and targeting ability is an ongoing endeavor. Herein, we report a simple and highly effective metal–phenolic assembly approach, whereby both ovalbumin (a model antigen) and immune-responsive metal ions (i.e., Al III and Mn II ) are immobilized within a biocompatible coordination network to form metal–phenolic network vaccines (MPNVs) under mild conditions. The MPNVs demonstrated specific lymph node accumulation and elicited humoral and cellular immune responses following their subcutaneous and intramuscular administration in mice. Mice immunized with MPNVs maintained a robust antibody response for at least 10 weeks, comparable to a commercial aluminum adjuvant. The modularity of the assembly approach afforded dual-metal incorporation into MPNVs (MPNV Mn+Al ), which amplified immune responses up to 11-fold compared to the mixture of OVA, Al III, and Mn II (i.e., OVA + Al + Mn). Moreover, MPNVs showed effective anticancer properties in suppressing the development of B16F10 melanoma in mice. Specifically, treatment with MPNV Mn+Al led to a 5-fold reduction in subcutaneous tumor volume and a 6.6-fold decrease in metastatic nodule number, compared to treatment with OVA + Al + Mn. This work provides insights into the immune activity of metal–organic materials, underpinning the rational design of vaccine and therapeutic platforms based on these materials.