Hu, Y., Gao, S., Lu, H., Tan, S., Chen, F., Ke, Y., & Ying, J. Y. (2023). A Self-Immolative DNA Nanogel Vaccine toward Cancer Immunotherapy. Nano Letters, 23(21), 9778–9787. https://doi.org/10.1021/acs.nanolett.3c02449
Abstract:
The development of precisely engineered vehicles for intracellular delivery and the controlled release of payloads remains a challenge. DNA-based nanomaterials offer a promising solution based on the A-T-G-C alphabet-dictated predictable assembly and high programmability. Herein, we present a self-immolative DNA nanogel vaccine, which can be tracelessly released in the intracellular compartments and activate the immune response. Three building blocks with cytosine-rich overhang domains are designed to self-assemble into a DNA nanogel framework with a controlled size. Two oligo agonists and one antigen peptide are conjugated to the building blocks via an acid-labile chemical linker. Upon internalization into acidic endosomes, the formation of i-motif configurations leads to dissociation of the DNA nanogel vaccine. The acid-labile chemical linker is cleaved, releasing the agonists and antigen in their traceless original form to activate antigen-presenting cells and an immune response. This study presents a novel strategy for constructing delivery platforms for intracellularly stimuli-triggered traceless release of therapeutics.
License type:
Publisher Copyright
Funding Info:
This research / project is supported by the A*STAR - Career Development Fund
Grant Reference no. : C210112014
This research / project is supported by the Science and Engineering Research Council, A*STAR - Central Research Fund
Grant Reference no. : UIBR, KIMR220901aSERCRF
This research / project is supported by the A*STAR - Health and Biomedical Sciences Industry Alignment Fund Pre-Positioning (IAF-PP)
Grant Reference no. : H20C6a0034