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However, achieving high encapsulation efficiencies without compromising nanoparticle stability and biocompatibility remains a key challenge for these bio-based delivery systems. In this context, bovine serum albumin (BSA) NPs crosslinked with genipin were developed as green and biocompatible nanocarriers with tunable physicochemical properties. The synthesis conditions were systematically optimized by varying reaction time, temperature, and the BSA:genipin ratio, with 24 h at room temperature and a 10:1 ratio yielding the most suitable NPs in terms of formation and colloidal stability. The optimized BSA NPs were then used to encapsulate sertraline and 5-fluorouracil, achieving encapsulation efficiencies of 82% and 40%, respectively. These results highlight the ability of this nanoplatform to incorporate bioactive compounds with distinct physicochemical characteristics, with the sertraline-loaded NPs showing particularly high loading efficiency for an albumin-based system. In vitro assays performed on normal prostate epithelial cells (PNT-2) and prostate cancer cells (22Rv1) showed that the BSA NPs modulated drug-induced cytotoxicity relative to free drugs, indicating a formulation-dependent biological response. These findings highlight the potential of genipin-crosslinked BSA NPs as a versatile and sustainable platform for drug delivery in cancer therapy.<\/jats:p>","DOI":"10.3390\/nano16171086","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T01:05:26Z","timestamp":1788224726000},"page":"1086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bovine Serum Albumin Nanoparticles Prepared with Genipin: Size Modulation, Encapsulation, and In Vitro Response"],"prefix":"10.3390","volume":"16","author":[{"given":"Beatriz","family":"Teixeira","sequence":"first","affiliation":[{"name":"CESAM-Center for Environmental and Marine Studies, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-4021","authenticated-orcid":false,"given":"M\u00f3nica","family":"Almeida","sequence":"additional","affiliation":[{"name":"CESAM-Center for Environmental and Marine Studies, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-141X","authenticated-orcid":false,"given":"Carolina","family":"Fraz\u00e3o","sequence":"additional","affiliation":[{"name":"CESAM-Center for Environmental and Marine Studies, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2699-646X","authenticated-orcid":false,"given":"Ana Violeta","family":"Gir\u00e3o","sequence":"additional","affiliation":[{"name":"CICECO-Aveiro Institute of Materials, Department of Materials and Ceramic Engineering, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0974-4853","authenticated-orcid":false,"given":"Adriana C. 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