{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:15:42Z","timestamp":1788282942004,"version":"build-2803163510"},"reference-count":378,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Enterprises and Made in Italy","award":["B89J23001360005"],"award-info":[{"award-number":["B89J23001360005"]}]},{"name":"TecnoMed Puglia","award":["B84I18000540002"],"award-info":[{"award-number":["B84I18000540002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Cancer remains a major global health challenge, and the limitations of conventional therapies, including systemic toxicity, drug resistance, and poor tumor selectivity, continue to drive the development of advanced nanomedicine strategies. In this context, nanocarriers offer promising opportunities to improve pharmacokinetics, enhance tumor accumulation, and enable controlled or stimuli-responsive drug release. Among them, inorganic nanoparticles (NPs) have gained considerable attention because of their structural stability, tunable surface chemistry, and multifunctional capabilities. Their performance depends on a structure\u2013property\u2013function relationship in which composition, morphology, porosity, degradability, and surface characteristics strongly influence interactions at the nano\u2013bio interface. This review examines the main classes of nanoplatforms currently explored for cancer therapy, including inorganic, polymeric, lipid-based, and hybrid organic\u2013inorganic systems. Particular attention is given to the trade-offs that define each platform in terms of loading capacity, biodegradability, multifunctionality, and translational potential. The discussion also highlights the role of predictive biological models, emphasizing that 3D spheroids, organoids, and organ-on-chip systems provide more realistic insights than conventional 2D assays for evaluating tumor penetration and microenvironment-responsive delivery. In addition, the review considers emerging directions in AI-guided nanoparticle engineerization design and natural-compound-based nanomedicines, both of which are expanding the therapeutic landscape. Overall, the field is moving toward more integrated, application-specific, and clinically translatable nanomedicine platforms capable of addressing the complex biological barriers of cancer treatment.<\/jats:p>","DOI":"10.3390\/ma19173729","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:28:22Z","timestamp":1788280102000},"page":"3729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer Drug Delivery with Nanoparticles and Biomolecules: Stimuli-Responsive, Theranostic, and AI-Guided Approaches"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0354-384X","authenticated-orcid":false,"given":"Chiara","family":"Boncristiani","sequence":"first","affiliation":[{"name":"Experimental Medicine Department, University of Salento, Via Monteroni, 73100 Lecce, Italy"},{"name":"Institute of Nanotechnology (CNR NANOTEC), Consiglio Nazionale delle Ricerche, S. P. 6 Lecce-Monteroni SNC, 73100 Lecce, Italy"},{"name":"Tecnomed Puglia\u2014Technopole for Precision Medicine (Biotech Lecce Hub), c\/o Ecotekne Campus, via Monteroni, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3328-7701","authenticated-orcid":false,"given":"Francesca","family":"Baldassarre","sequence":"additional","affiliation":[{"name":"Institute of Nanotechnology (CNR NANOTEC), Consiglio Nazionale delle Ricerche, S. P. 6 Lecce-Monteroni SNC, 73100 Lecce, Italy"},{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM), Via G. Giusti 9, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"Eddahaoui","sequence":"additional","affiliation":[{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM), Via G. Giusti 9, 50121 Florence, Italy"},{"name":"Laboratory of Physical Chemistry of Applied Materials LCPMA, Faculty of Sciences Ben M\u2019Sick, Hassan II University of Casablanca, B.P. 7955 Bd Cdt Driss El Harti, Casablanca 20702, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4467-0922","authenticated-orcid":false,"given":"Giuseppe","family":"Ciccarella","sequence":"additional","affiliation":[{"name":"Institute of Nanotechnology (CNR NANOTEC), Consiglio Nazionale delle Ricerche, S. P. 6 Lecce-Monteroni SNC, 73100 Lecce, Italy"},{"name":"National Interuniversity Consortium of Materials Science and Technology (INSTM), Via G. Giusti 9, 50121 Florence, Italy"},{"name":"Department of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, S. 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