In vivo Gold Nanoparticle Delivery of Peptide Vaccine Induces Anti-Tumor Immune Response in Prophylactic and Therapeutic Tumor Models

被引:171
作者
Almeida, Joao Paulo Mattos [1 ]
Lin, Adam Yuh [1 ]
Figueroa, Elizabeth Raquel [1 ]
Foster, Aaron Edward [2 ]
Drezek, Rebekah Anna [1 ]
机构
[1] Rice Univ, Dept Bioengn, Houston, TX 77005 USA
[2] Bellicum Pharmaceut, Houston, TX USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
TARGETING DENDRITIC CELLS; CPG OLIGONUCLEOTIDES; SUPPRESSOR-CELLS; BIODISTRIBUTION; CONJUGATION; EXPRESSION; INDUCTION; MULTIPLE; NANORODS; LIVER;
D O I
10.1002/smll.201402179
中图分类号
O6 [化学];
学科分类号
070301 [无机化学];
摘要
Gold nanoparticles (AuNPs) are promising vehicles for cancer immunotherapy, with demonstrated efficacy in immune delivery and innate cell stimulation. Nevertheless, their potential has yet to be assessed in the in vivo application of peptide cancer vaccines. In this study, it is hypothesized that the immune distribution and adjuvant qualities of AuNPs could be leveraged to facilitate delivery of the ovalbumin (OVA) peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a B16-OVA tumor model. AuNP delivery of OVA (AuNP-OVA) and of CpG (AuNP-CpG) enhanced the efficacy of both agents and induced strong antigen-specific responses. In addition, it is found that AuNP-OVA delivery alone, without CpG, is sufficient to promote significant antigen-specific responses, leading to subsequent anti-tumor activity and prolonged survival in both prophylactic and therapeutic in vivo tumor models. This enhanced therapeutic efficacy is likely due to the adjuvant effect of peptide coated AuNPs, as they induce inflammatory cytokine release when cultured with bone marrow dendritic cells. Overall, AuNP-mediated OVA peptide delivery can produce significant therapeutic benefits without the need of adjuvant, indicating that AuNPs are effective peptide vaccine carriers with the potential to permit the use of lower and safer adjuvant doses during vaccination.
引用
收藏
页码:1453 / 1459
页数:7
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