{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:48:17Z","timestamp":1782535697798,"version":"3.54.5"},"reference-count":39,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Municipal Natural Science Foundation","award":["7202123"],"award-info":[{"award-number":["7202123"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF\/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide method and Michael addition reaction, respectively. Subsequently, self-assembled nanoparticles were formed from the carrier and curcumin under specific conditions. The materials were characterized by spectroscopy, chromatography, elemental analysis, energy-dispersive spectroscopy and X-ray diffraction. The efficacy of the formulation was evaluated in two cell lines, ARPE-19 and HUVEC-T1. In addition, the pharmacological mechanism was explored using transcriptome sequencing as a complementary approach. Key Findings: Self-assembled nanoparticles were successfully prepared by combining the two modified carrier materials, PCL-PEG-MF and PCL-PEG-cRGDfc, with curcumin. The nanoparticles exhibited an encapsulation efficiency of 78.09%, a particle size of 162.33 nm, and a zeta potential of \u221223.28 mV and displayed a spherical morphology. They showed sustained release in simulated physiological conditions and stronger affinity for ARPE-19 cells under oxidative stress. Nearly 100% of the nanoparticles were internalized by the cells, which was accompanied by reduced ROS and LDH release and decreased DNA fragmentation. In addition, the nanoparticles inhibited neovascularization by reducing VEGF-A release, thereby potentially protecting the retina in macular degeneration and reducing choroidal hemorrhage. Further analyses showed that curcumin and its nanoformulations significantly reduced the expression of inflammatory factors such as IL-1\u03b2 and IL-18, lowered the protein levels of Caspase-1, GSDMD-N, and NLRP3, and increased AMPK levels. Conclusions: Using PCL-PEG as the carrier framework, MF and cRGDfc were conjugated to construct a curcumin-loaded nanoparticle with retinal-targeting capability. This nanoparticle, characterized by a small particle size, sustained release, and targeted delivery to retinal pigment epithelium (RPE) cells under oxidative stress, alleviated oxidative stress-induced damage. Its therapeutic effect may be mediated, at least in part, by interference with the AMPK\/mTOR pathway and activation of the NLRP3\/Caspase-1\/GSDMD pathway.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060761","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin and cRGDfc-Modified Nanoparticles Loaded with Curcumin for Age-Related Macular Degeneration: In Vitro Pharmacodynamics and Molecular Mechanisms"],"prefix":"10.3390","volume":"18","author":[{"given":"Juan","family":"Liu","sequence":"first","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5807-9104","authenticated-orcid":false,"given":"Ziheng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchang","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Yi","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiman","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nannan","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-1626","authenticated-orcid":false,"given":"Xingbin","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxv","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Ni","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhai","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global Prevalence of Age\u2013Related Macular Degeneration and Disease Burden Projection for 2020 and 2040: A Systematic Review and Meta\u2013Analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. 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