{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T09:03:01Z","timestamp":1785488581878,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["ZR2021QH299"],"award-info":[{"award-number":["ZR2021QH299"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Colorectal cancer (CRC) is a major clinical challenge due to high metastasis and therapy resistance. Photodynamic therapy (PDT) offers precise tumor ablation but lacks sustained anti-metastatic activity. Peptidic urokinase-type plasminogen activator (uPA) inhibitors suppress metastasis but suffer from short half-life and poor tumor retention. This study aimed to develop a dual-functional self-assembled nanoplatform integrating PDT and selective uPA inhibition for synergistic CRC treatment. Methods: We designed and synthesized a conjugate by linking pyropheophorbide-a (PPA) with uPA-targeted cyclic peptide IG2, which self-assembled into nanoparticles (PINPs). Physicochemical properties, reactive oxygen species (ROS) generation, and uPA inhibitory activity were characterized. In vitro studies included cellular uptake, cytotoxicity, and invasion assays. In vivo therapeutic efficacy was evaluated in subcutaneous CT26 tumor models and lung metastasis models, with biosafety assessed by body weight monitoring. Results: PINPs exhibited uniform spherical nanostructure, prolonged blood circulation, and enhanced tumor accumulation via the enhanced permeability and retention (EPR) effect. Under 680 nm irradiation, PINPs generated robust ROS and induced tumor cell apoptosis. PINPs potently inhibited uPA activity and suppressed tumor cell invasion. In vivo, PINPs plus PDT achieved significant tumor growth inhibition (73.6%) and strong anti-metastatic efficacy (60.7%), superior to free IG2. No obvious systemic toxicity was observed. Conclusions: The dual-functional PINPs achieve short-term acute tumor ablation via PDT and sustained anti-metastatic potential via uPA inhibition within the tested observation windows, with favorable biosafety. This carrier-free self-assembly strategy provides proof-of-concept validation and a generalizable design paradigm for developing synergistic anti-metastatic nanotherapeutics against metastatic CRC.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080948","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:46:41Z","timestamp":1785487601000},"page":"948","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual-Functional Self-Assembled Nanoparticles for Synergistic Photodynamic Therapy and Antimetastatic Treatment of Colorectal Cancer"],"prefix":"10.3390","volume":"18","author":[{"given":"Yixuan","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261053, China"},{"name":"School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haokun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261053, China"},{"name":"School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinghai","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261053, China"},{"name":"School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4512-3131","authenticated-orcid":false,"given":"Ruifeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261053, China"},{"name":"School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261053, China"},{"name":"School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4415-1102","authenticated-orcid":false,"given":"Dong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Shandong Second Medical University, Weifang 261053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3968-7279","authenticated-orcid":false,"given":"Peng","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1700","DOI":"10.1016\/S2214-109X(23)00406-0","article-title":"Quantitative estimates of preventable and treatable deaths from 36 cancers worldwide: A population-based study","volume":"11","author":"Frick","year":"2023","journal-title":"Lancet Glob. 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