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Despite these benefits, most nanomedicines require intravenous or other invasive administration routes, leading to safety and patient compliance concerns that hinder clinical translation. Oral delivery represents an ideal drug administration method due to its convenience and the protective barrier provided by the gastrointestinal tract, which enhances safety and compliance. However, challenges such as low drug solubility, limited permeability of the gastrointestinal barrier, and the harsh acid-base and enzymatic environment of the gastrointestinal tract significantly impact the efficacy and application of oral nanomedicines. Additionally, reduced bioavailability resulting from first-pass hepatic metabolism after gastrointestinal absorption through the venous plexus presents a major technical obstacle for orally administered nanomedicines. This review introduces design strategies for oral nanomedicines using a function-oriented approach and summarizes the characteristics of various nanomedicine types based on structural similarities and differences. Several representative oral nanomedicines developed in recent years are highlighted, with a focus on their applications to specific diseases. The review also discusses the potential and current limitations of oral nanomedicines that must be addressed to facilitate future clinical translation. The primary objective is to provide a comprehensive analysis of oral drug administration from multiple perspectives and to offer valuable insights for clinical application.<\/jats:p>","DOI":"10.1021\/acsbiomaterials.6c00341","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T04:06:49Z","timestamp":1789358809000},"page":"4591-4610","source":"Crossref","is-referenced-by-count":0,"title":["Current Advancements of Orally Administered Nanomedicine: Disease Diagnosis and Therapy via Targeted Delivery"],"prefix":"10.1021","volume":"12","author":[{"given":"Yonghao","family":"Hu","sequence":"first","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250021"]},{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University , , , ,","place":["Jinan, Shandong, China, 250021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250021"]},{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University , , , ,","place":["Jinan, Shandong, China, 250021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University , , , ,","place":["Jinan, Shandong, China, 250021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wu","sequence":"additional","affiliation":[{"name":"Shandong First Medical University , , , ,","place":["Jinan, Shandong, China, 250117"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chong","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University , , , ,","place":["Jinan, Shandong, China, 250021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0879-2507","authenticated-orcid":true,"given":"Zhe","family":"Dong","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University , , , ,","place":["Jinan, Shandong, China, 250021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Shang","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250021"]},{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University , , , ,","place":["Jinan, Shandong, China, 250021"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leping","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong University , , , ,","place":["Jinan, Shandong, China, 250021"]},{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University , , , ,","place":["Jinan, Shandong, China, 250021"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"issue":"3","key":"2026091400064262100_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103498","article-title":"Global, regional, and national burden of inflammatory bowel disease and its associated anemia, 1990 to 2019 and predictions to 2050: An analysis of the global burden of disease study 2019","volume":"23","author":"Wang","year":"2024","journal-title":"Autoimmun. 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