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Here, we use 3D Single-Molecule Active-feedback Real-time Tracking (3D-SMART) microscopy to resolve nanoparticle dynamics in agarose gels with unprecedented spatiotemporal resolution. We highlight \u2018hopping diffusion\u2019, where particles intermittently escape confinement pockets, providing insights into hydrogel microstructure. Long, highly sampled trajectories enable extraction of kinetic parameters, confinement sizes, and thermodynamic barriers. This study demonstrates 3D-SMART\u2019s ability to probe particle-environment interactions at super-resolution (\u223c10 nm in XY and \u223c30 nm in Z) in 3D, offering new perspectives on nanoparticle diffusion and the structural dynamics of porous materials, with implications for drug delivery, material science, and biological systems.<\/jats:p>\n                <jats:sec>\n                  <jats:title>ToC figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"643103v3_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.13.643103","type":"posted-content","created":{"date-parts":[[2025,3,16]],"date-time":"2025-03-16T04:45:23Z","timestamp":1742100323000},"source":"Crossref","is-referenced-by-count":1,"title":["Super-resolving particle diffusion heterogeneity in porous hydrogels via high-speed 3D active-feedback single-particle tracking microscopy"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-6215","authenticated-orcid":false,"given":"Yuxin","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Chemistry, Duke University, 124 Science Dr., Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8075-7831","authenticated-orcid":false,"given":"Haoting","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University, 124 Science Dr., Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3180-279X","authenticated-orcid":false,"given":"Kevin D.","family":"Welsher","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Duke University, 124 Science Dr., Durham, NC 27708, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041205544306000_2025.03.13.643103v3.1","doi-asserted-by":"publisher","DOI":"10.1088\/0034-4885\/78\/12\/124601"},{"key":"2026041205544306000_2025.03.13.643103v3.2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00815"},{"key":"2026041205544306000_2025.03.13.643103v3.3","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24152826"},{"key":"2026041205544306000_2025.03.13.643103v3.4","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.9b00692"},{"key":"2026041205544306000_2025.03.13.643103v3.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1223012"},{"key":"2026041205544306000_2025.03.13.643103v3.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(97)00059-8"},{"key":"2026041205544306000_2025.03.13.643103v3.7","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b03430"},{"key":"2026041205544306000_2025.03.13.643103v3.8","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b00019"},{"key":"2026041205544306000_2025.03.13.643103v3.9","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jhazmat.2016.06.065","volume":"318","year":"2016","journal-title":"J. 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