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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引用次数: 0
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 (E711–19) 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.
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.