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首页> 外文期刊>Biomaterials Science >In vivo targeting of DNA vaccines to dendritic cells using functionalized gold nanoparticles
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In vivo targeting of DNA vaccines to dendritic cells using functionalized gold nanoparticles

机译：使用官能化金纳米颗粒的DNA疫苗对树突疫苗的体内靶向

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The clinical success of dendritic cell (DC)-based genetic immunization remains critically dependent on the availability of effective and safe nano-carriers for targeting antigen-encoded DNA vaccines to DCs, the most potent antigen-presenting cells in the human body in vivo. Recent studies revealed the efficacies of mannose receptor-mediated in vivo DC-targeted genetic immunization by liposomal DNA vaccine carriers containing both mannose-mimicking shikimoyl and transfection enhancing guanidinyl functionalities. However, to date, the efficacies of this approach have not been examined for metal-based nanoparticle DNA vaccine carriers. Herein, we report for the first time, the design, synthesis, physico-chemical characterization and bioactivities of gold nanoparticles covalently functionalized with a thiol ligand containing both shikimoyl and guanidinyl functionalities (Au-SGSH). We show that Au-SGSH nanoparticles can deliver DNA vaccines to mouse DCs under in vivo conditions. Subcutaneous administration of near infrared (NIR) dye-labeled Au-SGSH showed significant accumulation of the NIR dye in the DCs of the nearby lymph nodes compared to that for the non-targeting NIR-labeled Au-GSH nanoconjugate containing only a covalently tethered guanidinyl group, not the shikimoyl-functionality. Under prophylactic settings, in vivo immunization (s.c.) with the Au-SGSH-pCMV-MART1 nanoplex induced a long-lasting (180 days) immune response against murine melanoma. Notably, mannose receptor-mediated in vivo DC-targeted immunization (s.c.) with the Au-SGSH-MART1 nanoplex significantly inhibited established melanoma growth and increased the overall survivability of melanoma-bearing mice under therapeutic settings. The Au-SGSH nanoparticles reported herein have potential use for in vivo DC-targeted genetic immunization against cancer and infectious diseases.
机译：树突细胞（DC）基因免疫的临床成功仍然依赖于用于靶向抗原编码的DNA疫苗的有效和安全的纳米载体的可用性，该纳米载体在体内人体中最有效的抗原呈递细胞。最近的研究表明，脂质体DNA疫苗载体含有甘露糖 - 模拟的shikimoyl和转染的胍啶型官能团的脂质体DNA疫苗载体的体内DC靶向遗传免疫的疗效。然而，迄今为止，尚未检查该方法的效果，但尚未检查金属基纳米颗粒DNA疫苗载体。在此，我们首次报告，用含有Shikimoyl和胍啶官能团（Au-Sgsh）的硫醇配体共价官能化的金纳米颗粒的设计，合成，物理化学表征和生物活性。我们表明AU-SGSH纳米粒子可以将DNA疫苗递送到体内病症的小鼠DC。近红外（NIR）染料标记的Au-Sgsh的皮下施用显示了与仅含有共价束缚的胍啶基的非靶向NIR标记的Au-GSH纳米缀合物相比，在附近的淋巴结的DC中显示出NIR染料的显着积累小组，不是shikimoyl功能。在预防性环境下，在体内免疫（S.C.）中，具有Au-Sgsh-PCMV-MART1纳米片诱导对小鼠黑素瘤的持久（180天）的免疫应答。值得注意的是，用Au-Sgsh-Mart1纳米人在体内DC靶标免疫（S.C.）中介导的甘养受体显着抑制了确立的黑色素瘤生长，并在治疗环境下提高了黑色素瘤小鼠的总体活力。本文报道的Au-Sgsh纳米颗粒具有针对癌症和传染病的体内DC靶向遗传免疫的潜在用途。

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