{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:21:00Z","timestamp":1790792460395,"version":"4.1.0"},"reference-count":129,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":44,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52173294"],"award-info":[{"award-number":["52173294"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["52473161"],"award-info":[{"award-number":["52473161"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wires.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["WIREs Nanomed Nanobiotechnol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The drug delivery nanosystems (DDNS) have demonstrated excellent potential in numerous drug modifications reliant on the physical and chemical properties. However, the main challenge in the clinical application transformation of DDNS lies in the biological barriers between the administration site and the target site, which hinders efficient drug transport. The polyethylene glycol (PEG)\u2010modified stealth strategies that have been clinically approved have also been questioned due to inherent defects such as accelerated blood clearance and specific immune responses. As an alternative to PEG, zwitterion polymers with characteristics including forming a strong hydration layer, extremely low immunogenicity, and ultra\u2010delayed blood circulation time have stood out in the surface modification of DDNS for various administration routes. This review introduces the biological barriers faced by drugs in various administration routes, elaborates on the advantages of the inherent properties of zwitterions in overcoming these barriers, and focuses on the latest progress in how zwitterions can flexibly modify DDNS to achieve superior delivery efficiency and efficacy in various administration routes. Finally, the rational design of zwitterion\u2010modified DDNS for future disease treatment is envisioned.<\/jats:p>\n                  <jats:p>\n                    This article is categorized under:\n                    <jats:list list-type=\"simple\">\n                      <jats:list-item>\n                        <jats:p>Therapeutic Approaches and Drug Discovery &gt; Emerging Technologies<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>","DOI":"10.1002\/wnan.70037","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T19:23:13Z","timestamp":1760556193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Rational Design of Zwitterionic Nanosystems to Overcome Biological Barriers for Drug Delivery by Various Administration Routes"],"prefix":"10.1002","volume":"17","author":[{"given":"Jiahui","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering, School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyue","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxian","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Energy and Mechanical Engineering Nanjing Normal University  Nanjing P. 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