{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:22:09Z","timestamp":1785410529940,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,9]]},"group-title":"Bioengineering","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"award":["R35GM133325"],"award-info":[{"award-number":["R35GM133325"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2342136"],"award-info":[{"award-number":["2342136"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The cytosolic delivery of therapeutic proteins remains one of the most persistent challenges in modern drug delivery. Here, we report the discovery and characterization of an encapsulin-based protein nanocage, QtEnc, with unexpected permeability properties and the ability to internalize cargo proteins\n                  <jats:italic>in vitro<\/jats:italic>\n                  , fundamentally departing from existing protein nanocage cargo loading paradigms. This permeability enables simple, rapid, and single-step post-assembly cargo loading, accommodating cargos as large as 482 kDa, and allowing multiplexed cargo co-encapsulation with tunable ratios. Leveraging this property, we develop a modular QtEnc-based NanoCarrier (QtEncNC) with a pH-responsive cargo detachment module and an endosomal escape module, enabling low pH-triggered cargo release from assembled shells and subsequent endosomal escape for cytosolic delivery. Using a cytotoxic protein, BLF1, as a proof-of-concept QtEncNC payload, we demonstrate efficient cytosolic protein delivery in HeLa cells. These findings establish QtEncNC as a versatile and modular platform for cytosolic protein delivery with broad biomedical potential.\n                <\/jats:p>","DOI":"10.64898\/2026.04.06.716810","type":"posted-content","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T18:20:15Z","timestamp":1775758815000},"source":"Crossref","is-referenced-by-count":1,"title":["A permeable protein nanocage enables facile cargo loading and cytosolic protein delivery"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0111-5219","authenticated-orcid":false,"given":"Seokmu","family":"Kwon","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109, USA"},{"name":"Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, 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