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In this work, a Design of Experiments approach was applied to optimize the synthesis of non-imprinted and imprinted PNE-NPs. A green, pH-triggered precipitation\/redispersion protocol was introduced for nanoparticle purification, providing fast and reproducible recovery without organic solvents, and surpassing conventional membrane dialysis methods, which are typically long and labor-intensive. Key parameters (pH, temperature, reaction time, stirring, and monomer concentration) were screened in H\n                      <jats:sub>2<\/jats:sub>\n                      O\/NaOH and TRIS buffer media. Optimized PNE-NPs displayed hydrodynamic diameters below 200\u00a0nm, spherical morphology, and negligible cytotoxicity in HaCaT keratinocytes across a broad concentration range. As a model study, PNE-NPs were imprinted against the Fc portion of human IgG1 and tested as synthetic receptors by surface plasmon resonance\u00a0(SPR). Two flow-mode immobilization strategies were compared on bare gold chips: covalent grafting on thiol-modified gold and direct adsorption. Both allowed real-time, in-flow monitoring and markedly improved affinity (K\n                      <jats:sub>D<\/jats:sub>\n                      \u2009&lt;\u200910\n                      <jats:sup>\u22128<\/jats:sup>\n                      \u00a0mol L\n                      <jats:sup>\u22121<\/jats:sup>\n                      ) compared to previous imprinted PNE nanofilms. The adsorption protocol stood out for its simplicity, high affinity and selectivity (\u03b1\u2009&gt;\u200927.4), and full in situ reconditioning of the SPR gold transducer with NaClO washes, enabling multiple reuse cycles. These results establish PNE-NPs as versatile synthetic receptors, highlighting their promise as next-generation platforms for diagnostics and therapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00604-026-07893-z","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:48:13Z","timestamp":1771519693000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biocompatible molecularly imprinted polynorepinephrine nanoparticles: rational design and one-step reversible immobilization for enhanced protein recognition by surface plasmon resonance"],"prefix":"10.1007","volume":"193","author":[{"given":"Simone","family":"Ventisette","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Galgani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Palladino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Citi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Minunni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Scarano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"7893_CR1","doi-asserted-by":"publisher","first-page":"629","DOI":"10.3390\/polym15030629","volume":"15","author":"S Akg\u00f6n\u00fcll\u00fc","year":"2023","unstructured":"Akg\u00f6n\u00fcll\u00fc S, K\u0131l\u0131\u00e7 S, Esen C, Denizli A (2023) Molecularly imprinted polymer-based sensors for protein detection. 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After using this tool\/service, the authors carefully reviewed and edited the content as needed and took full responsibility for the content of the publication.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declaration of generative AI and AI-assisted technologies in the writing process"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"171"}}