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Inspired by these bio\u2010geometries, we explore how nanoscale anisotropy can be engineered to control the dynamic transport and biodistribution of synthetic nanocarriers in the body. We fabricate anisotropic silica nanocapsules with precisely tunable asymmetry to dissect shape effects on nano\u2010bio interactions under physiological flow. Under shear flow in vitro, increasing anisotropy markedly reduced cellular uptake, whereas this effect was much less pronounced under static conditions, revealing strong flow\u2013shape coupling. In vivo, highly anisotropic nanocapsules exhibit prolonged circulation, with a 2.8\u2010fold longer half\u2010life than spherical counterparts and significantly reduced sequestration by the liver, spleen, and circulating blood cells. Mechanistic analyses attributed these effects to decreased phagocytic internalization by Kupffer cells, splenic macrophages, and circulating monocytes. Computational fluid dynamics simulations corroborated this phenomenon, demonstrating that greater anisotropy shifts particle trajectories away from vessel walls toward the central flow stream, lowering the chances of cellular interception. Together, these results establish nanoscale anisotropy as a critical determinant of nanoparticle transport, immune recognition, and clearance under flow. Anisotropy engineering therefore provides a nature\u2010inspired framework for designing long\u2010circulating, immune\u2010evasive nanocarriers with improved therapeutic performance.<\/jats:p>","DOI":"10.1002\/advs.77000","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:41:29Z","timestamp":1785937289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering Morphological Anisotropy to Control the In Vivo Transport Dynamics, Clearance, and Biodistribution of Silica Nanocarriers"],"prefix":"10.1002","author":[{"given":"Xiaofei","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs School of Medicine and Pharmacy Chinese Ministry of Education Ocean University of China  Qingdao People's Republic of China"},{"name":"Laboratory For Marine Drugs and Bioproducts Qingdao Marine Science and Technology Center  Qingdao People's Republic of 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