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The emergence of nanotechnology offers innovative strategies to create a diversity of nanoparticles (NPs) with intrinsic capacities of mimicking the functions of proteins. These artificial mimics are produced in a cost\u2010efficient and controllable manner, with their protein\u2010mimicking performances comparable or superior to those of natural proteins. Moreover, they can be endowed with additional functionalities that are absent in natural proteins, such as cargo loading, active targeting, membrane penetrating, and multistimuli responding. Therefore, protein\u2010mimicking NPs have been utilized more and more often in biosystems for a wide range of applications including detection, imaging, diagnosis, and therapy. To highlight recent progress in this broad field, herein, representative protein\u2010mimicking NPs that fall into one of the four distinct categories are summarized: mimics of enzymes (nanozymes), mimics of fluorescent proteins, NPs with high affinity binding to specific proteins or DNA sequences, and mimics of protein scaffolds. This review covers their subclassifications, characteristic features, functioning mechanisms, as well as the extensive exploitation of their great potential for biological and biomedical purposes. Finally, the challenges and prospects in future development of protein\u2010mimicking NPs are discussed.<\/jats:p>","DOI":"10.1002\/adma.202201562","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T17:23:55Z","timestamp":1652721835000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Protein\u2010Mimicking Nanoparticles in Biosystems"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9922-3746","authenticated-orcid":false,"given":"Xiaoyuan","family":"Ji","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes Center for Single\u2010Cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine  Shanghai 200025 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8146-5552","authenticated-orcid":false,"given":"Haiyun","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncogenes and Related Genes Center for Single\u2010Cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine  Shanghai 200025 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhai","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational Medicine Shanghai Jiao Tong University  Shanghai 200240 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.1c09281"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190094"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201805368"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202110432"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar2000327"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-017-0056"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.8b10527"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9MH00388F"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja304118z"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c11245"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202001718"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b07734"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03198-9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2021.101269"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CS00457A"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/C8CS00718G"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00672"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.9b00140"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1246\/cl.1987.405"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200460446"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn102592h"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.10.010"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201405105"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201813771"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.8b05552"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b01616"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201801484"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202106967"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.1c10732"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02502-3"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07257-z"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.9b03782"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b17945"},{"key":"e_1_2_9_34_1","first-page":"1616","volume":"12","author":"Cai S. 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