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Adv."],"published-print":{"date-parts":[[2026,6,12]]},"abstract":"<jats:p>\n                    Systemic metabolic disorders such as diabetes and hyperuricemia demand multiorgan therapeutic intervention, yet single-target therapies often fail to restore homeostasis. Here, we present an orally administered, multistage-targeted nanoplatform (P1P2NPs) for the sequential delivery of therapeutic peptides to distinct organs. P1P2NPs is composed of a bioresponsive polymer poly(\u03b2-amino ester)-disulfide bond-poly(carboxybetaine) (PAE-SS-PCB), 1,2-distearoyl-\n                    <jats:italic toggle=\"yes\">sn<\/jats:italic>\n                    -glycero-3-phosphoethanolamine-block poly(carboxybetaine) (DSPE-PCB) and Eudragit L100-55, designed to release peptide P2 (Val-Pro-Tyr-Pro-Gln) in the intestine for dipeptidyl peptidase-IV (DPP-IV) inhibition, while hepatic-targeted peptide P1(Pro-Pro-Lys-Asn-Trp) is selectively liberated in the liver to suppress xanthine oxidase (XOD). Fabricated through sequential emulsification and layer-by-layer assembly, P1P2NPs exhibit spatiotemporal control over drug release, enabling precise modulation of intestinal and hepatic metabolic pathways. In a murine model of diabetic-hyperuricemia comorbidity, the nanoplatform demonstrated synergistic efficacy by normalizing glucose and uric acid levels through multiorgan targeting. This work establishes a paradigm for spatially controlled peptide delivery, offering a versatile strategy for treating complex metabolic diseases.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef3323","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:58:42Z","timestamp":1781114322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Programmed oral delivery of peptide therapeutics for multiorgan targeting in metabolic disorders of hyperglycemia and hyperuricemia"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0723-0637","authenticated-orcid":true,"given":"Junyu","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China."},{"name":"Key Laboratory of Bioactive Proteins and Peptides Green 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Graduate School, Tsinghua University, Shenzhen 518055, China."},{"name":"Key Laboratory of Bioactive Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education Institutes, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China."},{"name":"Key Laboratory of Bioactive Proteins and Peptides Green Biomanufacturing of Guangdong Higher Education Institutes, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua 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