Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy

被引:432
作者
Kim, Jaeyun [1 ,2 ,3 ]
Li, Weiwei Aileen [1 ,2 ]
Choi, Youngjin [3 ]
Lewin, Sarah A. [2 ]
Verbeke, Catia S. [1 ,2 ]
Dranoff, Glenn [4 ,5 ]
Mooney, David J. [1 ,2 ]
机构
[1] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[2] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA
[3] Sungkyunkwan Univ, Sch Chem Engn, Suwon, South Korea
[4] Dana Farber Canc Inst, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Boston, MA USA
基金
新加坡国家研究基金会; 美国国家科学基金会; 美国国家卫生研究院;
关键词
MESOPOROUS SILICA NANOPARTICLES; DENDRITIC CELLS; NALP3; INFLAMMASOME; DRUG-DELIVERY; T-FH; ANTIGEN; RESPONSES; INNATE; BIOMATERIALS; DEGRADATION;
D O I
10.1038/nbt.3071
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Implanting materials in the body to program host immune cells is a promising alternative to transplantation of cells manipulated ex vivo to direct an immune response, but doing so requires a surgical procedure. Here we demonstrate that high-aspect-ratio, mesoporous silica rods (MSRs) injected with a needle spontaneously assemble in vivo to form macroporous structures that provide a 3D cellular microenvironment for host immune cells. In mice, substantial numbers of dendritic cells are recruited to the pores between the scaffold rods. The recruitment of dendritic cells and their subsequent homing to lymph nodes can be modulated by sustained release of inflammatory signals and adjuvants from the scaffold. Moreover, injection of an MSR-based vaccine formulation enhances systemic helper T cells T(H)1 and T(H)2 serum antibody and cytotoxic T-cell levels compared to bolus controls. These findings suggest that injectable MSRs may serve as a multifunctional vaccine platform to modulate host immune cell function and provoke adaptive immune responses.
引用
收藏
页码:64 / U241
页数:11
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