{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:53:47Z","timestamp":1791546827542,"version":"4.3.4"},"reference-count":165,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":38,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["wires.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["WIREs Nanomed Nanobiotechnol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Despite significant progress in cancer immunotherapy, challenges such as limited immune activation, tumor immune evasion, low response rates in solid tumors and off\u2010target effects continue to hinder therapeutic efficacy. These challenges necessitate strategies to remodel the immune\u2010suppressive tumor microenvironment (TME) into an immune activated state. Over the past decade, nanotechnology\u2010based cancer immunotherapies have gained considerable attention for their ability to modulate the TME and stimulate immune responses. Among these, DNA nanotechnology\u2010based systems have emerged as highly promising candidates due to their inherent immunomodulatory, biodegradable, and biocompatible properties. This review discusses recent advances in DNA nanostructures including tetrahedrons, nanotubes, nanocages, spherical nucleic acids (SNAs), DNA hybrid nanomaterials and DNA\/RNA hybrids, highlighting their immunotherapeutic mechanisms and potential to enhance cellular uptake, immune cell targeting and activation of key pathways. Preclinical studies demonstrate that DNA nanostructures such as DNA tetrahedrons can induce immunogenic cell death, endoplasmic reticulum stress, and dendritic cell maturation, while DNA nanovaccines and CpG\u2010functionalized DNA origami activate TLR9 and STING pathways to enhance cytotoxic T lymphocyte (CTL) and antigen\u2010presenting cell (APC) responses. Furthermore, DNA hydrogels and DNA\u2013metal hybrids enable controlled drug delivery and immune stimulation. In this review, different DNA\u2010based nanostructures have been discussed with their immunotherapeutic mechanism, emphasizing their potential to transform immune modulation strategies and overcome the challenges associated with conventional cancer therapies.<\/jats:p>\n                  <jats:p>\n                    This article is categorized under:\n                    <jats:list list-type=\"simple\">\n                      <jats:list-item>\n                        <jats:p>Nanotechnology Approaches to Biology &gt; Nanoscale Systems in Biology<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Therapeutic Approaches and Drug Discovery &gt; Nanomedicine for Oncologic Disease<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Biology\u2010Inspired Nanomaterials &gt; Nucleic Acid\u2010Based Structures<\/jats:p>\n                      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