A DNA Nanodevice for Cancer Vaccination
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doi: 10.1007/s40242-020-0325-6
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A DNA Nanodevice for Cancer Vaccination ZUO Hua1* and MAO Chengde2* 1. College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, P. R. China ; 2. Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States Abstract To realize effective cancer immunotherapy, Ding et al. constructed a structurally well-defined DNA-based nanodevice to quantitatively assemble cancer cell-specific antigen and multiple adjuvants as a cancer vaccine. This nanodevice vaccine can efficiently accumulate in the draining lymph nodes and respond to the endosomal acidic environment of dendritic cells to release the antigen and adjuvants. These active payloads stimulate dendritic cells maturation and antigen presentation to elicit a robust, antigen-specific cytotoxic T-lymphocyte response to kill cancer cells. This work has been published online in the Nature Materials on Sept.7, 2020. DNA molecules, the information carriers, have been demonstrated as excellent building blocks to fabricate programmable nanostructures based on Watson-Crick base-pairing rules and their well-established secondary structure, double helix[1,2]. After about. 40 years of exploration, DNA nanotechno- logy is now being utilized to develop nanomaterials with practical functionalities and applications. These advances have a remarkable impact on the biological applications of DNA nanostructures[3], most notably in drug delivery for cancer treatment. In a previous report, Ding and his coworkers[4] constructed a DNA origami-based nanorobot for selective occlusion of tumor blood vessels to combat cancers. They fabricated a DNA nano-vehicle to deliver thrombin molecules into tumor vessels to induce onsite thrombosis and tumor necrosis, demonstrating the first safe use of intravenously injected nanorobot for effec-
Fig.1
tive tumor therapy. Building on this work, more recently, Ding and his colleagues[5] designed a novel DNA origami-based nanodevice vaccine to trigger tumor-specific T-cell activation and kill cancer cells(Fig.1). Cancer immunotherapy, including immune checkpoint inhibitors, engineered chimeric antigen receptor T-cells(CAR-T) and vaccines, holds tremendous promise for improving cancer treatment. A major challenge in cancer immunotherapy is efficient vaccine delivery for stimulating a robust tumor-specific T-cell response in a controlled manner. For efficient delivery of antigen peptide and molecular adjuvants(CpG DNA and double-stranded RNA) in the draining lymph nodes(dLNs), a tube-shaped DNA origami nanodevice was assembled to position antigen and adjuvants inside its inner cavity, protecting these molecular cargoes from interfering with the external environment. The integration of low pH-responsive, DNA locking
Schematic illustration of the tumor antigen peptide/CpG/dsRNA-co-loaded DNA nanodevice for cancer immunotherapy
The DNA nanodevice can efficiently enter dendritic cells(DCs), reconfigure its conformation in the acidic endosomal environment within endosomes, and
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