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Proteins are safer than synthetic nanocarriers due to their greater biocompatibility and the absence of toxic degradation products. In this context, ferritin has the additional benefit of inherently targeting the membrane receptor transferrin 1, which is overexpressed by most cancer cells. Furthermore, this self\u2010assembling multimeric protein can be loaded with more than 2000 iron atoms, as well as drugs, contrast agents, and other cargos. However, recombinant ferritin currently costs ~3.5\u2009million\u2009\u20ac\u2009g\n                    <jats:sup>\u22121<\/jats:sup>\n                    , presumably because the limited number of producers cannot meet demand, making it generally unaffordable as a nanocarrier. Because plants can produce proteins at very\u2010large\u2010scale, we developed a simple, proof\u2010of\u2010concept process for the production of the human ferritin heavy chain\u00a0by transient expression in\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    . We optimized the protein yields by screening different compartments and 5\u2032\u2010untranslated regions in PCPs, and selected the best\u2010performing construct for production in differentiated plants. We then established a rapid and scalable purification protocol by combining pH and heat treatment before extraction, followed by an ultrafiltration\/diafiltration size\u2010based separation process. The optimized process achieved ferritin levels of ~40\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    fresh biomass although depth filtration limited product recovery to ~7%. The purity of the recombinant product was &gt;90% at costs ~3% of the current sales price. Our method therefore allows the production of affordable ferritin heavy chain as a carrier for therapeutic and diagnostic agents, which is suitable for further stability and functionality testing in vitro and in vivo.\n                  <\/jats:p>","DOI":"10.1002\/bit.28312","type":"journal-article","created":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T22:39:13Z","timestamp":1671575953000},"page":"1038-1054","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Simple plant\u2010based production and purification of the assembled human ferritin heavy chain as a nanocarrier for tumor\u2010targeted drug delivery and bioimaging in cancer therapy"],"prefix":"10.1002","volume":"120","author":[{"given":"Matthias","family":"Kn\u00f6dler","sequence":"first","affiliation":[{"name":"Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Fraunhofer\u2010Gesellschaft zur F\u00f6rderung der angewandten Forschung e. 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