{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:55:25Z","timestamp":1786978525957,"version":"build-2736575974"},"reference-count":58,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003784"],"award-info":[{"award-number":["82003784"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2682024ZTPY007"],"award-info":[{"award-number":["2682024ZTPY007"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Protease\u2010activated receptor 2 (PAR2) widely modulates various cytokine secretions and inflammatory responses, while excessive cytokine releases and immune hyperactivation may trigger cytokine storm. However, the potential participation of PAR2 in cytokine storm remains elusive. CRISPR\u2010Cas9 as an efficient gene editing tool can be used for investigating the possible function of PAR2. In this study, albumin\u2010based nanoparticles (hAlbumin\/cgPAR2) to protect and deliver CRISPR\u2010Cas9 for precise gene editing of PAR2 is constructed. Nanosized albumin largely assisted CRISPR\u2010Cas9\u2010PAR2 (cgPAR2) to enter cells via scavenger receptor\u2010mediated endocytosis, and then triggered potent transfection efficiency, consequently stimulating PAR2 knockout in vitro and in vivo. Apart from delivering CRISPR\u2010Cas9, nanosized albumin could be colocalized with TLR4 on endosome and promote PAR2 deficiency to attenuate TLR4\/NF\u2010\u03baB signaling, exerting the strong inhibitory effect of albumin in inflammatory responses depending on TLR4. Moreover, PAR2 deficiency induced by hAlbumin\/cgPAR2 alleviated ERK\/STING\/NLRP3 signaling and GSDMD\u2010mediated pyroptosis, consequently inhibiting cytokine storm. Therefore, this study uncovered dual functions of nanosized albumin in delivering CRISPR\u2010Cas9 and facilitating PAR2 deficiency to prevent cytokine storm. It also uncovered that the significant role of PAR2 in modulating cytokine storm and provided a potential gene therapy strategy for treating this disease.<\/jats:p>","DOI":"10.1002\/smll.202405593","type":"journal-article","created":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T23:56:08Z","timestamp":1733097368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dual\u2010functional Nanosized Albumin Facilitates CRISPR\u2010Cas9\u2010PAR2 to Mitigate Cytokine Storm via TLR4 and Pyroptosis Signaling"],"prefix":"10.1002","volume":"21","author":[{"given":"Jianbin","family":"Li","sequence":"first","affiliation":[{"name":"Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Qi","sequence":"additional","affiliation":[{"name":"Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canquan","family":"Mao","sequence":"additional","affiliation":[{"name":"Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5120-9475","authenticated-orcid":false,"given":"Yuhong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and Engineering Southwest Jiaotong University  Chengdu 610031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/VIW.20210003"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24360-w"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15332"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2021"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2023.07.049"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2021.119144"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20170272"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804800200"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.03.053"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.02.004"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202207448"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.09.012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0090-8"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202102051"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202300665"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20210081"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113891"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2016.1193149"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.12.057"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3330"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ntm.2024.100036"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00153"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2023.08.013"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.10.017"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2023.13147"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax5135"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.201900101"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai9044"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.5b00153"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2005.04.006"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.07.006"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2007.08.007"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.222421399"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46130-0"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI136042"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2023.2261556"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202108476"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45615-2"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-020-1643-8"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1538-9"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050511"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1863"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3921"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112185"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01036-5"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c00227"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.09.002"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2021.06.001"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.105051"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c07632"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi5934"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2022.04.003"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.02.042"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101781"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.6b01088"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15514"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02172-2"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202405593","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T09:16:20Z","timestamp":1755162980000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.202405593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12]]},"references-count":58,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/smll.202405593"],"URL":"https:\/\/doi.org\/10.1002\/smll.202405593","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12]]},"assertion":[{"value":"2024-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2405593"}}