{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:17:59Z","timestamp":1787807879064,"version":"build-2784847793"},"reference-count":43,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009570","name":"Srinakharinwirot University","doi-asserted-by":"publisher","award":["450\/2025"],"award-info":[{"award-number":["450\/2025"]}],"id":[{"id":"10.13039\/100009570","id-type":"DOI","asserted-by":"publisher"}]},{"award":["450\/2025"],"award-info":[{"award-number":["450\/2025"]}],"id":[{"id":"https:\/\/ror.org\/04718hx42","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Colorectal cancer therapy requires drug delivery systems that improve treatment efficacy and minimize systemic toxicity. In this study, chitosan-based nanoparticles were fabricated and functionalized with folic acid (FA), phenylalanine (PA), and butyric acid (BA) to enhance the delivery of curcumin to Caco-2 cancer cells. The nanoparticles were prepared using an ionic gelation method, and their physicochemical properties, cellular uptake efficiency, and cytotoxicity\u2014including safety evaluation against normal HIEC-6 cells\u2014were investigated. Results showed that ligand conjugation significantly influenced the physicochemical properties of the nanoparticles. CRFANP (FA-modified) exhibited the largest particle size (263.5 nm) due to its rigid aromatic structure, while CRPANP (PA-modified) showed an intermediate size (138.0 nm) and the lowest surface charge (15.59 mV). In contrast, CRBANP (BA-modified) presented the smallest particle size (128.2 nm) and the highest positive surface charge (23.27 mV). These distinct physicochemical properties directly influenced their cellular interactions; CRBANP and CRFANP showed higher uptake than CRPANP, with CRBANP yielding the maximum accumulation of curcumin in Caco-2 (21.92 nM\/mg protein) and HT-29 cells (22.09 nM\/mg protein). Correlating with the uptake data, cytotoxicity assays revealed that CRBANP was the most potent formulation, exhibiting the lowest IC50 of 1.30 \u00b5M in Caco-2 cells, which was significantly lower than that of CRFANP (3.49 \u00b5M) and CRPANP (7.40 \u00b5M), while demonstrating high selectivity against Caco-2 cells with an SI of 46.5 and no apparent toxicity toward normal HIEC-6 cells. This enhanced efficacy is attributed to the synergistic action of butyric acid as a histone deacetylase inhibitor (HDACi), which complements curcumin\u2019s anticancer activity. These findings indicate that integrating butyric acid into chitosan nanoparticles provides an effective and selective strategy for targeted colorectal cancer therapy.<\/jats:p>","DOI":"10.3390\/polym18172064","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:01:07Z","timestamp":1787670067000},"page":"2064","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Curcumin-Loaded Ligand-Conjugated Chitosan Nanoparticles: A Comparative Study of Folic Acid, Phenylalanine, and Butyric Acid Conjugates for Colorectal Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1000-6729","authenticated-orcid":false,"given":"Chayut","family":"Fongsuk","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Srinakharinwirot University, Ongkharak Campus, Nakhon Nayok 26120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chutwadee","family":"Krisanapun","sequence":"additional","affiliation":[{"name":"Department of Biopharmacy, Faculty of Pharmacy, Srinakharinwirot University, Ongkharak Campus, Nakhon Nayok 26120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duangratana","family":"Shuwisitkul","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Srinakharinwirot University, Ongkharak Campus, Nakhon Nayok 26120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Roshandel, G., Ghasemi-Kebria, F., and Malekzadeh, R. 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