Extracellular Silica Nanomatrices Promote In Vitro Maturation of Anti-Tumor Dendritic Cells Via Activation of Focal Adhesion Kinase

The efficacy of dendritic cell (DC)–based cancer vaccines is critically determined by the functionalities of <i>in vitro </i>maturated DCs. The maturation of DCs typically relies on chemicals that are cytotoxic or hinder the ability of DCs to efficiently activate the antigen–specific cytotoxic T–lymphocytes (CTLs) against tumor. Herein, we replace the maturation chemicals with extracellular silica nanomatrices, fabricated by glancing angle deposition, to promote <i>in vitro</i> maturation of murine bone marrow–derived DCs (mBMDCs). The extracellular nanomatrices composed of silica nanozigzags (NZs) enable the generation of mature mBMDCs with upregulated levels of co–stimulatory molecules, CCR7, XCR1, DC-SIGN, and enhanced endocytic capacity. The <i>in vitro</i> maturation is partially governed by focal adhesion kinase that is mechanically activated in the curved cell adhesions formed at the DC–NZ interfaces. The NZ–maturated mBMDCs can prime the antigen–specific CTLs into PD–1^lowCD44^high memory phenotypes <i>in vitro</i> and suppress the growth of tumors <i>in vivo</i>. Meanwhile, the NZ–mediated beneficial effects are also observed in human monocyte–derived DCs. This work demonstrates that the silica NZs promote the anti–tumor capacity of <i>in vitro</i> maturated DCs via the mechanoactivation of FAK, supporting the potential of silica NZs being a promising biomaterial for cancer immunotherapy.