Self‐Assembled Two‐Dimensional Chiral Meso‐Topography Determines the Balance of Cellular and Humoral Immunity Against Tumors
Abstract
ABSTRACT The development of nanomaterials‐based cancer vaccines has broadened the scope of immunotherapy. Nanomaterials with characteristics such as chirality, 2D, and flexibility have attracted widespread attention because they can maximize the interface between the materials and immune cells. Here, we report the fabrication of 2‐D mesoporous silica nanodisks with a chiral meso‐topography as vaccine adjuvants. These uniform nanodisks, with diameters from 200 nm to 1 µm, possess unique spiral mesoporous patterns of ∼ 10 nm. The thickness of the chiral mesoporous nanodisks can be precisely controlled in units of one layer (∼ 7 nm), thereby achieving precise regulation in surface topology, dimension and flexibility. The unique 2‐D chiral mesoporous structure originates from the maximum occupancy of confined space of micellar helical arrangement, which is distinct from conventional methods based on internal tension. The combination of flexibility, 2‐D structure and chirality enhances nanodisks’ interaction with dendritic cells (DCs), significantly improving DC maturation via Toll‐like receptors/Nuclear Factor‐kappa B (TLR/NF‐κB), Mitogen‐Activated Protein Kinase (MAPK) and Focal Adhesion Kinase (FAK) signaling pathways. Upon nanovaccines’ activation of DCs in vivo, DCs further presents antigen for activating T cells to trigger balanced cellular and humoral immunity. Subcutaneous injection of the nanodisks‐adjuvanted cancer vaccine can significantly inhibit the tumor growth and extend the survival of melanoma‐bearing mice to more than 60 days, about three times higher than that of the PBS‐treated group. When combined with PD‐1 antibody, the cancer vaccines maximize tumor suppression, achieving a tumor‐free outcome in one‐third of the cases.
Article Details
Authors (16)
Lingkai Dong
College of Smart Materials and Future Energy Department of Chemistry Laboratory of Advanced Materials Fudan University Shanghai 200433 P.R. China
Wei Yang
Xingjin Li
Laboratory of Advanced Materials Aqueous Battery Center Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials Collaborative Innovation Center of Chemistry for Energy Materials Shanghai Wusong Laboratory of Materials Science College of Smart Materials and Future Energy Fudan University Shanghai P. R. China
Yanming Ma
Xirui Huang
College of Chemistry and Materials, Department of Chemistry, Department of Macromolecular Science, Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Chemistry for Energy Materials (2011-ChEM)
Yu Fan
Nan Cao
Department of Applied Physics
Qianqian Lu
College of Sciences
Yating Zhan
Department of Chemistry, Shanghai Stomatological Hospital & School of Stomatology, State Key Laboratory of Molecular Engineering of Polymers, iChem (Collaborative Innovation Center of Chemistry for Energy Materials), Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials
Jiacheng Shen
Minchao Liu
Liang Chen
Yu Chen
Meihua Yu
Materdicine Lab, School of Life Sciences
Tiancong Zhao
Department of Chemistry, Shanghai Stomatological Hospital & School of Stomatology, State Key Laboratory of Molecular Engineering of Polymers, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials
Dongyuan Zhao
Laboratory of Advanced Materials, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, State Key Laboratory of Porous Materials for Separation and Conversion, Fudan University, 220 Handan, Shanghai 200433, P. R. China