Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles

查看全文 作　　者：Jiawei [1]Wu;Liyun [1]Xing;Yaxian [1]Zheng;Yinglan [1]Yu;Ruinan [1]Wu;Xi [1]Liu;Lian [1]Li;Yuan [1]Huang

机构地区：[1]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu 610041,China

出　　处：《Acta Pharmaceutica Sinica B》索引2023年第13卷第9期,共16页

基　　金：financial support from the National Natural Science Foundation of China(No.81872818);the National Key R&D Program of China(No.2021YFE0115200)。 摘　　要：Protein corona(PC)has been identified to impede the transportation of intravenously injected nanoparticles(NPs)from blood circulation to their targeted sites.However,how intestinal PC(IPC)affects the delivery of orally administered NPs are still needed to be elucidated.Here,we found that IPC exerted“positive effect”or“negative effect”depending on different pathological conditions in the gastrointestinal tract.We prepared polystyrene nanoparticles(PS)adsorbed with different IPC derived from the intestinal tract of healthy,diabetic,and colitis rats(H-IPC@PS,D-IPC@PS,C-IPC@PS).Proteomics analysis revealed that,compared with healthy IPC,the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine.Consequently,both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking,which increased the transcytosis from the epithelium.Together,disease-specific IPC endowed NPs with higher intestinal absorption.D-IPC@PS posed“positive effect”on intestinal absorption into blood circulation for diabetic therapy.Conversely,CIPC@PS had“negative effect”on colitis treatment because of unfavorable absorption in the intestine before arriving colon.These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases. 关键词：Oral nanoparticles Pathological intestine Disease-specific Intestinal protein corona Proteomics analysis Intracellular trafficking Transepithelial transport Intestinal absorption

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Disease-specific protein corona formed in pathological intestine enhances the oral absorption of nanoparticles

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