AIM： TO identify the differentially expressed miRNAs and their targets in hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC）. METHODS： Six hundred and sixty seven human miRNAs were quantitatively ...AIM： TO identify the differentially expressed miRNAs and their targets in hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC）. METHODS： Six hundred and sixty seven human miRNAs were quantitatively analyzed by Taqman lowdensity miRNA array （TLDA） in HBV-HCC tissues. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses were used to analyze the significant function and pathway of the differentially expressed miRNAs in HBV-HCC. TargetScan software was used to predict the targets of deregulated miRNAs. Western blotting and luciferase assay were performed to verify the targets of these miRNAs.RESULTS： Ten up-regulated miRNAs （miR-217, miR- 518b, miR-517c, miR-520g, miR-519a, miR-522, miR- 518e, miR-525-3p, miR-512-3p, and miR-518a-3p） and 11 down-regulated miRNAs （miR-138, miR-214, miR-214#, miR-199a-5p, miR-433, miR-511, miR-592, miR-483-3p, miR-483-5p, miR-708 and miR-1275） were identified by Taqman miRNAs array and confirmed quantitatively by reverse transcription polymerase chain reaction in HCC and adjacent non-tumor tissues. GO and KEGG pathway analysis revealed that ＂regulation of actin cytoskeleton＂ and ＂pathway in cancer＂ are most likely to play critical roles in HCC tumorigenesis. MiR- 519a and ribosomal protein S6 kinase polypeptide 3 （RPS6KA3） were predicted as the most significant can-didates by miRNA-mRNA network. In addition, cyclin D3 （CCND3） and clathrin heavy chain （CHC）, usually up-regulated in HCC tissues, were validated as the di- rect target of miR-138 and miR-199a-5p, respectively.展开更多
Endocytosis occurs at the cell surface and involves internalization of the plasma membrane （PM） along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milie...Endocytosis occurs at the cell surface and involves internalization of the plasma membrane （PM） along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milieu and also serves to regulate various processes initiated at the cell surface. These include nutrient uptake, signaling from cell- surface receptors, and many other processes essential for cell and tissue functioning in metazoans. It is also central to the maintenance of PM lipid and protein homeostasis. There are multiple means of internalization that operate concurrently, at the cell surface. With advancement in high-resolution visualization techniques, it is now possible to track multiple endocytic cargo at the same time, revealing a remarkable diversity of endocytic processes in a single cell. A combination of live cell imaging and efficient genetic manipulations has also aided in understanding the functional hierarchy of molecular players in these mechanisms of internalization. Here we provide an account of various endocytic routes, their mechanisms of operation and occurrence across phyla.展开更多
Transforming growth factor-β （TGF-β） signaling is tightly regulated to ensure its proper physiological functions in different cells and tissues. Like other cell surface receptors, TGF-β receptors are internalized...Transforming growth factor-β （TGF-β） signaling is tightly regulated to ensure its proper physiological functions in different cells and tissues. Like other cell surface receptors, TGF-β receptors are internalized into the cell, and this process plays an important regulatory role in TGF-β signaling. It is well documented that TGF-β receptors are endocytosed via clathrin-coated vesicles as TGF-β endocytosis can be blocked by potassium depletion and the GTPasedeficient dynamin K44A mutant. TGF-β receptors may also enter cells via cholesterol-rich membrane microdomain lipid rafts/caveolae and are found in caveolin-l-positive vesicles. Although receptor endocytosis is not essential for TGF-β signaling, clathrin-mediated endocytosis has been shown to promote TGF-β-induced Smad activation and transcriptional responses. Lipid rafts/caveolae are widely regarded as signaling centers for G protein-coupled recep- tors and tyrosine kinase receptors, but they are indicated to facilitate the degradation of TGF-β receptors and there- fore turnoff of TGF-β signaling. This review summarizes current understanding of TGF-β receptor endocytosis, the possible mechanisms underlying this process, and the role of endocytosis in modulation of TGF-β signaling.展开更多
Influenza A virus H5N1 presents a major threat to human health. The entry of influenza virus into host cells is believed to be mediated by hemagglutinin (HA), a virus surface glycoprotein that can bind terminal sialic...Influenza A virus H5N1 presents a major threat to human health. The entry of influenza virus into host cells is believed to be mediated by hemagglutinin (HA), a virus surface glycoprotein that can bind terminal sialic acid residues on host cell glycoproteins and glycolipids. In this study, we elucidated the pathways through which H5N1 enters human lung carcinoma cell line A549. We first proved that H5N1 can enter A549 cells via endocytosis, as lysosomotropic agents, such as bafilomycin A1 and chloroquine, can rescue H5N1-induced A549 cell death. By using specific inhibitors, and siRNAs that target the clathrin pathway, we further found that H5N1 could enter A549 cells via clathrin-mediated endocytosis, while inhibitors targeting caveolae-mediated endocytosis could not inhibit H5N1 cell entry. These findings expand our understanding of H5N1 pathogenesis and provide new information for anti-viral drug research.展开更多
Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies...Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies to confirm the specific endocytic pathways and discusses factors for pathway selection.In addition,some intriguing implication about nanomedicine design based on endocytosis will also be discussed at the end.This review may provide new thoughts for the design of novel multifunctional nanomedicines.展开更多
The establishment of auxin maxima by PIN-FORMED 3 （PIN3）- and AUXIN RESISTANT l/LIKE AUX1 （LAX） 3 （AUX1/LAX3）-mediated auxin transport is essential for hook formation in Arabidopsis hypocotyls. Until now, howeve...The establishment of auxin maxima by PIN-FORMED 3 （PIN3）- and AUXIN RESISTANT l/LIKE AUX1 （LAX） 3 （AUX1/LAX3）-mediated auxin transport is essential for hook formation in Arabidopsis hypocotyls. Until now, however, the underlying regulatory mechanism has remained poorly understood. Here, we show that loss of function of clathrin light chain CLC2 and CLC3 genes enhanced auxin maxima and thereby hook curvature, alleviated the inhibitory effect of auxin overproduction on auxin maxima and hook curva- ture, and delayed blue light-stimulated auxin maxima reduction and hook opening. Moreover, pharmaco- logical experiments revealed that auxin maxima formation and hook curvature in clc2 clc3 were sensitive to auxin efflux inhibitors 1-naphthylphthalamic acid and 2,3,5-triiodobenzoic acid but not to the auxin influx inhibitor 1-naphthoxyacetic acid. Live-cell imaging analysis further uncovered that loss of CLC2 and CLC3 function impaired PIN3 endocytosis and promoted its lateralization in the cortical cells but did not affect AUX1 localization. Taken together, these results suggest that clathrin regulates auxin maxima and thereby hook formation through modulating PIN3 localization and auxin efflux, providing a novel mechanism that integrates developmental signals and environmental cues to regulate plant skotomorphogenesis and photomorphogenesis.展开更多
GGGGCC repeat expansions in the C9 ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia(c9 ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9 ORF72 ...GGGGCC repeat expansions in the C9 ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia(c9 ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9 ORF72 produce five dipeptide repeat(DPR) proteins by an unconventional repeat-associated non-ATG(RAN)translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs(poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5 Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase(JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PRinduced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependentendocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides.展开更多
Foot-and-mouth disease(FMD)is a highly contagious and economically important disease,which is caused by the FMD virus(FMDV).Although the cell receptor for FMDV has been identified,the specific mechanism of FMDV intern...Foot-and-mouth disease(FMD)is a highly contagious and economically important disease,which is caused by the FMD virus(FMDV).Although the cell receptor for FMDV has been identified,the specific mechanism of FMDV internalization after infection remains unknown.In this study,we found that kinesin family member 5B(KIF5B)plays a vital role during FMDV internalization.Moreover,we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation(Co-IP)and co-localization in FMDV-infected cells.In particular,the stalk[amino acids(aa)413–678]domain of KIF5B was indispensable for KIF5B-VP1 interaction.Moreover,overexpression of KIF5B dramatically enhanced FMDV replication;consistently,knockdown or knockout of KIF5B suppressed FMDV replication.Furthermore,we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating.KIF5B also promotes the transmission of viral particles to early and late endosomes during the early stages of infection.In conclusion,our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular transport.This study may provide a new therapeutic target for developing FMDV antiviral drugs.展开更多
In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical role...In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 （AdipoR1） and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K^＋ trapped AdipoR1 at the plasma membrane, and K^＋ depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K^＋ and overexpression of Eps15 mutants enhance adiponectin- stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might down-regulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5- dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.展开更多
Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different m...Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different magnitudes and patterns of shear stress(SS)generated by blood flow could engulf NPs in the blood.However,an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies.Here,the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted.The mechanism of SS affecting NP uptake through regulating the cellular ROS level,endothelial glycocalyx and membrane fluidity is summarized,and the molecules containing clathrin and caveolin in the engulfment process are elucidated.SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine.This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.展开更多
基金Supported by The Key Programs of the Ministry of Science and Technology, No. 2012ZX10002009-004Shanghai Leading Academic Discipline Project (B901)Science Fund for Creative Research Groups, NSFC, China, No. 30921006
文摘AIM： TO identify the differentially expressed miRNAs and their targets in hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC）. METHODS： Six hundred and sixty seven human miRNAs were quantitatively analyzed by Taqman lowdensity miRNA array （TLDA） in HBV-HCC tissues. Gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analyses were used to analyze the significant function and pathway of the differentially expressed miRNAs in HBV-HCC. TargetScan software was used to predict the targets of deregulated miRNAs. Western blotting and luciferase assay were performed to verify the targets of these miRNAs.RESULTS： Ten up-regulated miRNAs （miR-217, miR- 518b, miR-517c, miR-520g, miR-519a, miR-522, miR- 518e, miR-525-3p, miR-512-3p, and miR-518a-3p） and 11 down-regulated miRNAs （miR-138, miR-214, miR-214#, miR-199a-5p, miR-433, miR-511, miR-592, miR-483-3p, miR-483-5p, miR-708 and miR-1275） were identified by Taqman miRNAs array and confirmed quantitatively by reverse transcription polymerase chain reaction in HCC and adjacent non-tumor tissues. GO and KEGG pathway analysis revealed that ＂regulation of actin cytoskeleton＂ and ＂pathway in cancer＂ are most likely to play critical roles in HCC tumorigenesis. MiR- 519a and ribosomal protein S6 kinase polypeptide 3 （RPS6KA3） were predicted as the most significant can-didates by miRNA-mRNA network. In addition, cyclin D3 （CCND3） and clathrin heavy chain （CHC）, usually up-regulated in HCC tissues, were validated as the di- rect target of miR-138 and miR-199a-5p, respectively.
文摘Endocytosis occurs at the cell surface and involves internalization of the plasma membrane （PM） along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milieu and also serves to regulate various processes initiated at the cell surface. These include nutrient uptake, signaling from cell- surface receptors, and many other processes essential for cell and tissue functioning in metazoans. It is also central to the maintenance of PM lipid and protein homeostasis. There are multiple means of internalization that operate concurrently, at the cell surface. With advancement in high-resolution visualization techniques, it is now possible to track multiple endocytic cargo at the same time, revealing a remarkable diversity of endocytic processes in a single cell. A combination of live cell imaging and efficient genetic manipulations has also aided in understanding the functional hierarchy of molecular players in these mechanisms of internalization. Here we provide an account of various endocytic routes, their mechanisms of operation and occurrence across phyla.
基金The work in Ye-Guang Chen＇s laboratory is supported by grants from the National Natural Science Foundation of China （30430360, 30671033） and the Ministry of Sciences and Technology of China 973 Program （2004CB720002, 2006CB943401, 2006CB910102） and 863 Program （2006AA02Z 172）.
文摘Transforming growth factor-β （TGF-β） signaling is tightly regulated to ensure its proper physiological functions in different cells and tissues. Like other cell surface receptors, TGF-β receptors are internalized into the cell, and this process plays an important regulatory role in TGF-β signaling. It is well documented that TGF-β receptors are endocytosed via clathrin-coated vesicles as TGF-β endocytosis can be blocked by potassium depletion and the GTPasedeficient dynamin K44A mutant. TGF-β receptors may also enter cells via cholesterol-rich membrane microdomain lipid rafts/caveolae and are found in caveolin-l-positive vesicles. Although receptor endocytosis is not essential for TGF-β signaling, clathrin-mediated endocytosis has been shown to promote TGF-β-induced Smad activation and transcriptional responses. Lipid rafts/caveolae are widely regarded as signaling centers for G protein-coupled recep- tors and tyrosine kinase receptors, but they are indicated to facilitate the degradation of TGF-β receptors and there- fore turnoff of TGF-β signaling. This review summarizes current understanding of TGF-β receptor endocytosis, the possible mechanisms underlying this process, and the role of endocytosis in modulation of TGF-β signaling.
基金Supported by the National Natural Science Foundation of China (Grant No. 30623009)National Basic Research Program of China (Grant No. 2005CB523000)
文摘Influenza A virus H5N1 presents a major threat to human health. The entry of influenza virus into host cells is believed to be mediated by hemagglutinin (HA), a virus surface glycoprotein that can bind terminal sialic acid residues on host cell glycoproteins and glycolipids. In this study, we elucidated the pathways through which H5N1 enters human lung carcinoma cell line A549. We first proved that H5N1 can enter A549 cells via endocytosis, as lysosomotropic agents, such as bafilomycin A1 and chloroquine, can rescue H5N1-induced A549 cell death. By using specific inhibitors, and siRNAs that target the clathrin pathway, we further found that H5N1 could enter A549 cells via clathrin-mediated endocytosis, while inhibitors targeting caveolae-mediated endocytosis could not inhibit H5N1 cell entry. These findings expand our understanding of H5N1 pathogenesis and provide new information for anti-viral drug research.
文摘Nanomedicines employ multiple endocytic pathways to enter cells.Their following fate is interesting,but it is not sufficient understood currently.This review introduces the endocytic pathways,presents new technologies to confirm the specific endocytic pathways and discusses factors for pathway selection.In addition,some intriguing implication about nanomedicine design based on endocytosis will also be discussed at the end.This review may provide new thoughts for the design of novel multifunctional nanomedicines.
文摘The establishment of auxin maxima by PIN-FORMED 3 （PIN3）- and AUXIN RESISTANT l/LIKE AUX1 （LAX） 3 （AUX1/LAX3）-mediated auxin transport is essential for hook formation in Arabidopsis hypocotyls. Until now, however, the underlying regulatory mechanism has remained poorly understood. Here, we show that loss of function of clathrin light chain CLC2 and CLC3 genes enhanced auxin maxima and thereby hook curvature, alleviated the inhibitory effect of auxin overproduction on auxin maxima and hook curva- ture, and delayed blue light-stimulated auxin maxima reduction and hook opening. Moreover, pharmaco- logical experiments revealed that auxin maxima formation and hook curvature in clc2 clc3 were sensitive to auxin efflux inhibitors 1-naphthylphthalamic acid and 2,3,5-triiodobenzoic acid but not to the auxin influx inhibitor 1-naphthoxyacetic acid. Live-cell imaging analysis further uncovered that loss of CLC2 and CLC3 function impaired PIN3 endocytosis and promoted its lateralization in the cortical cells but did not affect AUX1 localization. Taken together, these results suggest that clathrin regulates auxin maxima and thereby hook formation through modulating PIN3 localization and auxin efflux, providing a novel mechanism that integrates developmental signals and environmental cues to regulate plant skotomorphogenesis and photomorphogenesis.
基金supported by the National Natural Science Foundation of China (81761148024 and 31871023)the National Key Scientific R&D Program of China (2016YFC1306000)+1 种基金Suzhou Clinical Research Center of Neurological Disease (Szzx201503)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, China
文摘GGGGCC repeat expansions in the C9 ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia(c9 ALS/FTD). It has been reported that hexanucleotide repeat expansions in C9 ORF72 produce five dipeptide repeat(DPR) proteins by an unconventional repeat-associated non-ATG(RAN)translation. Within the five DPR proteins, poly-PR and poly-GR that contain arginine are more toxic than the other DPRs(poly-GA, poly-GP, and poly-PA). Here, we demonstrated that poly-PR peptides transferred into cells by endocytosis in a clathrin-dependent manner, leading to endoplasmic reticulum stress and cell death. In SH-SY5 Y cells and primary cortical neurons, poly-PR activated JUN amino-terminal kinase(JNK) and increased the levels of p53 and Bax. The uptake of poly-PR peptides by cells was significantly inhibited by knockdown of clathrin or by chlorpromazine, an inhibitor that blocks clathrin-mediated endocytosis. Inhibition of clathrin-dependent endocytosis by chlorpromazine significantly blocked the transfer of poly-PR peptides into cells, and attenuated poly-PRinduced JNK activation and cell death. Our data revealed that the uptake of poly-PR undergoes clathrin-dependentendocytosis and blockade of this process prevents the toxic effects of synthetic poly-PR peptides.
基金supported by the National Natural Sciences Foundation of China(No.32102639 and 32072831)the National Key Research and Development Program of China(No.2021YFD1800300)+5 种基金the Gansu Science Foundation for Distinguished Young Scholars(No.21JR7RA026)the Earmarked Fund for CARS-35,the Strategic Priority Research Program of the National Center of Technology Innovation for Pigs(No.NCTIP-XD/C03)the Science and Technology Major Project of Gansu Province(No.22ZD6NA001)the Natural Science Foundation of Gansu Province(No.22JR5RA034 and 23JRRA549)the open competition program of top ten critical priorities of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province(No.2023SDZG02)the Fundamental Research Funds for the Central Universities(No.lzujbky-2022-ey20).
文摘Foot-and-mouth disease(FMD)is a highly contagious and economically important disease,which is caused by the FMD virus(FMDV).Although the cell receptor for FMDV has been identified,the specific mechanism of FMDV internalization after infection remains unknown.In this study,we found that kinesin family member 5B(KIF5B)plays a vital role during FMDV internalization.Moreover,we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation(Co-IP)and co-localization in FMDV-infected cells.In particular,the stalk[amino acids(aa)413–678]domain of KIF5B was indispensable for KIF5B-VP1 interaction.Moreover,overexpression of KIF5B dramatically enhanced FMDV replication;consistently,knockdown or knockout of KIF5B suppressed FMDV replication.Furthermore,we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating.KIF5B also promotes the transmission of viral particles to early and late endosomes during the early stages of infection.In conclusion,our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular transport.This study may provide a new therapeutic target for developing FMDV antiviral drugs.
文摘In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 （AdipoR1） and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K^＋ trapped AdipoR1 at the plasma membrane, and K^＋ depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K^＋ and overexpression of Eps15 mutants enhance adiponectin- stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might down-regulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5- dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.
基金supported by the National Natural Science Foundation of China(12032007,31971242)to G.W.the Chongqing Science and Technology Bureau(cstc2019jcyj-zdxmX0028)to G.W.JinFeng Laboratory,Chongqing,China(jfkyjf202203001)to G.W.
文摘Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different magnitudes and patterns of shear stress(SS)generated by blood flow could engulf NPs in the blood.However,an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies.Here,the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted.The mechanism of SS affecting NP uptake through regulating the cellular ROS level,endothelial glycocalyx and membrane fluidity is summarized,and the molecules containing clathrin and caveolin in the engulfment process are elucidated.SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine.This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.
