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The nanoparticles (NPs) are coated with polyethylene glycol chains as gatekeepers to improve their physicochemical properties and control drug release through the cleavable disulfide bonds (S\u2013S) in a reductive environment. This study describes different chemical conditions to achieve the highest NPs\u2019 surface functionalization yield, exploring both multistep and one\u2010pot chemical functionalization strategies. The best formulation is used for covalent PNA conjugation via the S\u2013S bond reaching a loading degree of 306 \u00b1 25\u00a0\u00b5g\n                    <jats:sub>PNA<\/jats:sub>\n                    mg\n                    <jats:sup>\u22121<\/jats:sup>\n                    <jats:sub>DNPs<\/jats:sub>\n                    . These systems are used for in vitro studies to evaluate the kinetic release, biocompatibility, cellular uptake, and activity on different cancer cells expressing high levels of PD\u2010L1. The obtained results prove the safety of the NPs up to 200\u00a0\u00b5g mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    and their advantage for controlling and enhancing the PNA intracellular release as well as antitumor activity. Moreover, the downregulation of PD\u2010L1 observed only with MDA\u2010MB\u2010231 cancer cells paves the way for targeted immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/smll.202204732","type":"journal-article","created":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T23:40:42Z","timestamp":1662939642000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Development of Surface Chemical Strategies for Synthesizing Redox\u2010Responsive Diatomite Nanoparticles as a Green Platform for On\u2010Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent"],"prefix":"10.1002","volume":"18","author":[{"given":"Monica","family":"Terracciano","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  via D. 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Montesano 49 Naples 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Rea","sequence":"additional","affiliation":[{"name":"Institute of Applied Sciences and Intelligent Systems Unit of Naples National Research Council  via P. Castellino 111 Naples 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennaro","family":"Piccialli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  via D. Montesano 49 Naples 80131 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Institute of Applied Sciences and Intelligent Systems Unit of Naples National Research Council  via P. 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