Silica Nanoparticle as a Lymph Node Targeting Platform for Vaccine Delivery

被引:89
作者
An, Myunggi [1 ]
Li, Meng [1 ]
Xi, Jingchao [1 ]
Liu, Haipeng [1 ,2 ,3 ]
机构
[1] Wayne State Univ, Dept Chem Engn & Mat Sci, Detroit, MI 48202 USA
[2] Wayne State Univ, Dept Oncol, Detroit, MI 48201 USA
[3] Barbara Ann Karmanos Canc Inst, Tumor Biol & Microenvironm Program, Detroit, MI 48201 USA
关键词
silica nanoparticle; electrostatic binding; vaccine delivery; lymph node targeting; cancer; SUPPORTED LIPID-BILAYERS; CPG OLIGODEOXYNUCLEOTIDES; DENDRITIC CELLS; IMMUNE-RESPONSE; HOLE FORMATION; ANTIGEN; DESIGN; ADJUVANT; ACTIVATION; PARTICLES;
D O I
10.1021/acsami.7b06024
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Nanoparticles have emerged as the platform of choice to improve the efficacy and safety of subunit vaccines. A major challenge underlying the use of nanomaterials in vaccines lies in the particle designs that can efficiently target and activate the antigen-presenting cells, especially dendritic cells. Here we show a toll-like receptor 9 (TLR-9) agonist and antigen coloaded, silica nanoparticles (SiNPs) are able to accumulate in antigen presenting cells in the draining lymph nodes after injection. Vaccine loaded SiNPs led to dramatically enhanced induction of antigen-specific B and T cell responses as compared to soluble vaccines, which in turn drove a protective antitumoral immunity in a murine tumor model. Additionally, SiNP vaccines greatly reduced the production of systemic proinflammatory cytokines and completely abrogated splenomegaly, key systemic toxicities of TLR-9 agonists that limit their advances in clinical applications. Our results demonstrate that structure optimized silica nanocarriers can be used as an effective and safe platform for targeted delivery of subunit vaccines.
引用
收藏
页码:23466 / 23475
页数:10
相关论文
共 56 条
[1]   Nanoparticles in the clinic [J].
Anselmo, Aaron C. ;
Mitragotri, Samir .
BIOENGINEERING & TRANSLATIONAL MEDICINE, 2016, 1 (01) :10-29
[2]   CD8+ T cell efficacy in vaccination and disease [J].
Appay, Victor ;
Douek, Daniel C. ;
Price, David A. .
NATURE MEDICINE, 2008, 14 (06) :623-628
[3]   Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns [J].
Bachmann, Martin F. ;
Jennings, Gary T. .
NATURE REVIEWS IMMUNOLOGY, 2010, 10 (11) :787-796
[4]  
Baines J, 2003, CLIN CANCER RES, V9, P2693
[5]   Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs [J].
Ballas, ZK ;
Krieg, AM ;
Warren, T ;
Rasmussen, W ;
Davis, HL ;
Waldschmidt, M ;
Weiner, GJ .
JOURNAL OF IMMUNOLOGY, 2001, 167 (09) :4878-4886
[6]  
Black M, 2010, EXPERT REV VACCINES, V9, P157, DOI [10.1586/erv.09.160, 10.1586/ERV.09.160]
[7]   Targeting CpG oligonucleotides to the lymph node by nanoparticles elicits efficient antitumoral immunity [J].
Bourquin, Carole ;
Anz, David ;
Zwiorek, Klaus ;
Lanz, Anna-Lisa ;
Fuchs, Sebastian ;
Weigel, Sarah ;
Wurzenberger, Cornelia ;
von der Borch, Philip ;
Golic, Michaela ;
Moder, Stefan ;
Winter, Gerhard ;
Coester, Conrad ;
Endres, Stefan .
JOURNAL OF IMMUNOLOGY, 2008, 181 (05) :2990-2998
[8]   Lymph-borne CD8α+ dendritic cells are uniquely able to cross-prime CD8+ T cells with antigen acquired from intestinal epithelial cells [J].
Cerovic, V. ;
Houston, S. A. ;
Westlund, J. ;
Utriainen, L. ;
Davison, E. S. ;
Scott, C. L. ;
Bain, C. C. ;
Joeris, T. ;
Agace, W. W. ;
Kroczek, R. A. ;
Mowat, A. M. ;
Yrlid, U. ;
Milling, S. W. F. .
MUCOSAL IMMUNOLOGY, 2015, 8 (01) :38-48
[9]   From empiricism to rational design: a personal perspective of the evolution of vaccine development [J].
De Gregorio, Ennio ;
Rappuoli, Rino .
NATURE REVIEWS IMMUNOLOGY, 2014, 14 (07) :505-514
[10]   Implantable Silk Composite Microneedles for Programmable Vaccine Release Kinetics and Enhanced Immunogenicity in Transcutaneous Immunization [J].
DeMuth, Peter C. ;
Min, Younjin ;
Irvine, Darrell J. ;
Hammond, Paula T. .
ADVANCED HEALTHCARE MATERIALS, 2014, 3 (01) :47-58