{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:35:12Z","timestamp":1785418512436,"version":"3.56.0"},"reference-count":123,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of T\u00fcrkiye","doi-asserted-by":"publisher","award":["124C536"],"award-info":[{"award-number":["124C536"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"award":["124C536"],"award-info":[{"award-number":["124C536"]}],"id":[{"id":"https:\/\/ror.org\/04w9kkr77","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Presidency for Turks Abroad and Related Communities"},{"id":[{"id":"https:\/\/ror.org\/04axc5d15","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>RNA-based therapeutics are becoming increasingly important in oncology, particularly following the rapid development of mRNA technologies during the COVID-19 pandemic, but their success strongly depends on how efficiently they can be delivered to target cells. Microfluidic technologies have redefined the design and manufacturing of RNA-based nanocomplexes, as they enable precise control over physicochemical features that are critical for clinical translation in oncology. This review examines recent developments in microfluidic-assisted synthesis of RNA nanocarriers, with a focus on cancer applications. Through a detailed analysis of material systems, device architectures, and formulation strategies, we explore how laminar flow environments enable reproducible encapsulation, tunable particle size, and improved payload stability. We examine the microfluidic assembly of lipid nanoparticles and polymeric carriers for RNA delivery, highlighting strategies to enhance durability, bioavailability, and cellular uptake. Advancements in process optimization, including flow parameter refinement and inline monitoring, are discussed alongside the influence of device geometries on mixing dynamics and nucleation. Beyond formulation, we explore the integration of microfluidics with tumor-on-chip platforms to evaluate transport, penetration, and therapeutic response in physiologically relevant cancer models. By connecting technological innovation with preclinical application, this work outlines the trajectory toward next-generation, personalized RNA nanomedicines enabled by microfluidic precision.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060679","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:58:38Z","timestamp":1780473518000},"page":"679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microfluidic-Driven Assembly of RNA Nanocomplexes: Design, Process Control and Translational Perspectives in Oncology"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2829-4570","authenticated-orcid":false,"given":"Ronan Pinto Nobrega","family":"dos Santos","sequence":"first","affiliation":[{"name":"Nanotechnology Engineering Department (PENt), Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1181-4378","authenticated-orcid":false,"given":"Dana Celeste","family":"Betancourt Roldan","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, Ankara University, 06830 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6196-5007","authenticated-orcid":false,"given":"Muslum","family":"Guven","sequence":"additional","affiliation":[{"name":"Turkish Energy, Nuclear and Mineral Research Agency, Boron Research Institute, 06530 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2340-5556","authenticated-orcid":false,"given":"Lucas Campana","family":"Leite","sequence":"additional","affiliation":[{"name":"Chemical Engineering Department (PEQ), Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3863-6765","authenticated-orcid":false,"given":"Francisco Jacomine Madrid","family":"Furlan","sequence":"additional","affiliation":[{"name":"Nanotechnology Engineering Department (PENt), Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3462-1457","authenticated-orcid":false,"given":"Gabriel Rocha Mariano","family":"da Silva","sequence":"additional","affiliation":[{"name":"Nanotechnology Engineering Department (PENt), Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vit\u00f3ria Almeida Pessoa","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Nanotechnology Engineering Department (PENt), Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolline da Silva","family":"Capriglione","sequence":"additional","affiliation":[{"name":"Nanotechnology Engineering Department (PENt), Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2426-6080","authenticated-orcid":false,"given":"Josie Pereira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Nanotechnology Engineering Department (PENt), Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2631-1811","authenticated-orcid":false,"given":"Jos\u00e9 Carlos","family":"Pinto","sequence":"additional","affiliation":[{"name":"Chemical Engineering Department (PEQ), Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21941-594, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"E\u015f","sequence":"additional","affiliation":[{"name":"Biomedical Engineering Department, Ankara University, 06830 Ankara, T\u00fcrkiye"},{"name":"Integrated Technologies Application and Research Center, Ankara 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