DNA Anchoring Strength Directly Correlates with Spherical Nucleic Acid–Based HPV E7 Cancer Vaccine Potency

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2024-06-14 DOI:10.1021/acs.nanolett.4c01392

Jeongmin Hwang, Jasper Wilson Dittmar, Janice Kang, Tonatiuh Ocampo, Michael Evangelopoulos, Zhenyu Han, Sergej Kudruk, Jochen Lorch* and Chad A. Mirkin*,

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Abstract

Vaccination for cancers arising from human papillomavirus (HPV) infection holds immense potential, yet clinical success has been elusive. Herein, we describe vaccination studies involving spherical nucleic acids (SNAs) incorporating a CpG adjuvant and a peptide antigen (E7_11–19) from the HPV-E7 oncoprotein. Administering the vaccine to humanized mice induced immunity-dependent on the oligonucleotide anchor chemistry (cholesterol vs (C12)₉). SNAs containing a (C12)₉-anchor enhanced IFN-γ production >200-fold, doubled memory CD8⁺ T-cell formation, and delivered more than twice the amount of oligonucleotide to lymph nodes in vivo compared to a simple admixture. Importantly, the analogous construct with a weaker cholesterol anchor performed similar to admix. Moreover, (C12)₉-SNAs activated 50% more dendritic cells and generated T-cells cytotoxic toward an HPV⁺ cancer cell line, UM-SCC-104, with near 2-fold greater efficiency. These observations highlight the pivotal role of structural design, and specifically oligonucleotide anchoring strength (which correlates with overall construct stability), in developing efficacious therapeutic vaccines.

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DNA 锚定强度与球形核酸型 HPV E7 癌症疫苗的效力直接相关。

针对人类乳头瘤病毒（HPV）感染引起的癌症的疫苗接种具有巨大的潜力，但临床上一直未能取得成功。在此，我们介绍了结合了 CpG 佐剂和 HPV-E7 肿瘤蛋白多肽抗原（E711-19）的球形核酸（SNA）疫苗接种研究。给人源化小鼠注射疫苗后，其免疫力取决于寡核苷酸锚化学成分（胆固醇与 (C12)9）。与简单混合相比，含有 (C12)9 锚的 SNA 可使 IFN-γ 生成量提高 200 倍以上，使记忆 CD8+ T 细胞的形成增加一倍，并将两倍多的寡核苷酸输送到体内淋巴结。重要的是，胆固醇锚较弱的类似构建物与掺杂物的表现相似。此外，(C12)9-SNA 激活的树突状细胞增加了 50%，产生的 T 细胞对 HPV+ 癌细胞系 UM-SCC-104 具有细胞毒性，效率提高了近 2 倍。这些观察结果凸显了结构设计，特别是寡核苷酸锚定强度（与整体结构稳定性相关）在开发有效治疗疫苗中的关键作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.